Safe effect of shock wave therapy for Plantar Fascitis

Radial Extracorporeal Shock Wave Therapy Is Safe and Effective in the Treatment of Chronic Recalcitrant Plantar Fasciitis         Results of a Confirmatory Randomized Placebo-Controlled Multicenter Study     Ludger Gerdesmeyer,*†‡ MD, PhD, Carol Frey,§ MD, Johannes Vester,|| PhD, Markus Maier,¶ PhD, Lowell Weil Jr,# DPM, Lowell Weil Sr,# DPM, Martin Russlies,** PhD, John Stienstra,†† DPM, Barry Scurran,†† DPM, Keith Fedder,§ MD, Peter Diehl,‡‡ MD, Heinz Lohrer,§§ MD, Mark Henne,† MD, and Hans Gollwitzer,† MD From the †Department of Orthopedic and Traumatology, Technical University Munich, Klinikum Rechts der Isar, Germany, the ‡Department of Joint Arthroplasty and Clinical Science, Mare Clinic, Kiel, Germany, §Orthopedic Foot and Ankle Center, Manhattan Beach, California, ||IDV Data Analyses and Study Planning, Biometrics in Medicine, Gauting, Germany, the ¶Department of Orthopedics, Ludwig Maximilian University, Munich, Germany, the #Weil Foot and Ankle Institute, Des Plaines, Illinois, **University Schleswig Holstein, Campus Lübeck, Lübeck, Germany, the ††Department of Podiatry, The Permanente Medical Group Inc, Union City, California, the ‡‡Department of Orthopedics, University Rostock, Rostock, Germany, and the §§Institute of Sports medicine, Frankfurt am Main, Germany

Background: Radial extracorporeal shock wave therapy is an effective treatment for chronic plantar fasciitis that can be administered to outpatients without anesthesia but has not yet been evaluated in controlled trials.   Hypothesis: There is no difference in effectiveness between radial extracorporeal shock wave therapy and placebo in the treatment of chronic plantar fasciitis.   Study Design: Randomized, controlled trial; Level of evidence, 1.   Methods: Three interventions of radial extracorporeal shock wave therapy (0.16 mJ/mm2; 2000 impulses) compared with placebo were studied in 245 patients with chronic plantar fasciitis. Primary endpoints were changes in visual analog scale composite score from baseline to 12 weeks’ follow-up, overall success rates, and success rates of the single visual analog scale scores (heel pain at first steps in the morning, during daily activities, during standardized pressure force). Secondary endpoints were single changes in visual analog scale scores, success rates, Roles and Maudsley score, SF-36, and patients’ and investigators’ global judgment of effectiveness 12 weeks and 12 months after extracorporeal shock wave therapy.   Results: Radial extracorporeal shock wave therapy proved significantly superior to placebo with a reduction of the visual analog scale composite score of 72.1% compared with 44.7% (P = .0220), and an overall success rate of 61.0% compared with 42.2% in the placebo group (P = .0020) at 12 weeks. Superiority was even more pronounced at 12 months, and all secondary Out ome measures supported radial extracorporeal shock wave therapy to be significantly superior to placebo (P < .025, 1- sided). No relevant side effects were observed.   Conclusion: Radial extracorporeal shock wave therapy significantly improves pain, function, and quality of life compared with placebo in patients with recalcitrant plantar fasciitis.   Keywords: heel pain; plantar fasciitis; shock wave; lithotripsy; radial extracorporeal shock wave therapy

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Plantar fasciitis is the most common  cause  of heel pain and accounts for  approximately 11%  to 15%  of all foot symptoms   requiring  professional care   in   the   adult.1,4,28   The course  of the  disease is  typically self-limiting, and  about 90%  of patients are  successfully treated with nonsurgical measures.1,2,4   The   self-limiting  character of  the   disease also  explains the  relatively  high success rates observed in the  placebo   arm   of  double-blind, randomized,  controlled trials.1,2,4,8,25,28,38    Nevertheless, the   remaining   patients enter  a  state  of recalcitrant painful heel  syndrome, often requiring  operative intervention.1,2,4,8   Thereby,  operative treatments like fasciotomy have  shown  promising results but are often associated with long recovery times, and  ath letes  especially seek alternative treatment modalities that  allow for continued training.1,2,4,8

Extracorporeal  shock  wave   therapy (ESWT)  has   been introduced for the treatment of recalcitrant painful heel syndrome as  an  alternative to surgery, allowing fast  recovery times  without  the  necessity  of  reduced weight bearing  or immobilization.22,23,28,33,38    However,  randomized,  controlled trials  assessing ESWT  in  chronic  painful  heel  syndrome have   revealed contradictory results,  and  the  clinical effectiveness has  been discussed controversially.3-5,8,14,17,18,23,32  By reviewing the  published  trials it becomes  obvious  that  the different  treatment   parameters  of  ESWT   are of  utmost importance  for the  outcome  of  treatment.5,17,22,23,28   In this respect, especially  the  application  of  local  anesthesia  has  been shown  to reduce efficacy.19,30  Furthermore, higher energies have been associated with greater pain reduction.23,27,33

It becomes apparent that  pooling data  of different treatment protocols  in  meta-analyses  or systematic  reviews  is  critical.22,28,35  Therefore, in assessing the  effectiveness of ESWT in plantar  fasciitis,  only specific treatment protocols should be evaluated, and  results could not be generalized.

Radial ESWT (rESWT) has been introduced into medicine as an effective and easy method to apply shock wave technology.15,20It represents an alternative to focused shock wave treatment, allowing for a broader application. Radial shock waves are generated ballistic ally by accelerating a bullet to hit an  applicator, which transforms the  kinetic energy into radially expanding  shock waves.15,20   Compared with  these radial shock waves, the focused shock waves show deeper tis- sue  penetration with significantly  higher energies concentrated to a smaller focus.15,16,20,22,28  This  article reports on a randomized, controlled, and  double-blinded Food  and  Drug Administration   (FDA)  study evaluating the   efficacy  and safety  of  rESWT   in  patients with  chronic   painful  heel syndrome.

 

 

METHODS

 

Study Design and Follow-up

 

This double-blind, randomized, placebo-controlled trial with parallel group design was   conducted internationally at 3

 

Study centers in the United States and 5 study centers in Europe. Patient enrollment took place during an 11-month period. A  total of 254  patients  were randomly assigned to receive either rESWT  or placebo  treatment with concealed allocation in permuted blocks of 4 to 8, stratified by treatment center with  the  use  of  a  computer-generated  random  list (Rancode; idv Data Analysis and  Study Planning, Gauting, Germany). Concealment of randomization was guaranteed by nontransparent envelopes. Both patients and assessing physicians were blinded to randomization as well as to the evaluating physician. The trial was conducted as an FDA approval study. In designing the study, the authors adhered to the standardized guidelines of good clinical practice from the International Conference on Harmonization (ICH).11,12

After 3   shock wave    or placebo   interventions   were applied, patients were followed until the end of the follow-up 1 period (12 weeks after the last intervention). At this  visit,  the   participants’  response  to  treatment  was rated, and  patients who  showed  sufficient  response on a clinically relevant level continued the  follow-up 2 phase, which ended  12  months after the  last rESWT or placebo intervention.  If patients suffered from significant pain after intervention, deblinding on demand after 12 weeks was allowed to provide other treatment options outside the   trial   instead of   suffering   for 12   months.  These patients left the trial with the worst outcome, which was carried forward. All these “worst” data were carried for- ward and used for analysis.

 

 

Participants

 

Patients were recruited from the participating study sites and from community-based referring physicians (primary care physicians, podiatrists, orthopedic surgeons). Participants of all activity levels were  included and  were asked to  continue on  the  same   activity level   throughout the study, although activity level  at enrollment and  during the  study were  not  specifically  assessed. The   study was approved by the FDA and   the responsible independent institutional review boards. Written informed consent was obtained from all participants. A total of 495 patients with plantar heel pain were screened; 254 patients met enrollment criteria and were enrolled in the study. A total of 251 patients out of 254 were treated. The flow of participants through the study is displayed in Figure 1.

 

 

Inclusion Criteria

 

The   complete   inclusion criteria are listed in Appendix A (available online at http://ajs.sagepub.com/supplemental/). Inclusion criteria included a history of at least 6 months of chronic plantar painful heel syndrome that proved resist- ant   to nonsurgical treatment. Diagnosis was   confirmed clinically by physical examination with a typical point of

 

 

Study centers in the United States and 5 study centers in Europe. Patient enrollment took place during an 11-month period. A  total of 254  patients  were randomly assigned to receive either rESWT  or placebo  treatment with concealed allocation in permuted blocks of 4 to 8, stratified by treatment center with  the  use  of  a  computer-generated  random  list (Rancode; idv Data Analysis and  Study Planning, Gauting, Germany). Concealment of randomization was guaranteed by nontransparent envelopes. Both patients and assessing physicians were blinded to randomization as well as to the evaluating physician. The trial was conducted as an FDA approval study. In designing the study, the authors adhered to the standardized guidelines of good clinical practice from the International Conference on Harmonization (ICH).11,12

After 3   shock wave    or placebo   interventions   were applied, patients were followed until the end of the follow-up 1 period (12 weeks after the last intervention). At this  visit,  the   participants’  response  to  treatment  was rated, and  patients who  showed  sufficient  response on a clinically relevant level continued the  follow-up 2 phase, which ended  12  months after the  last rESWT or placebo intervention.  If patients suffered from significant pain after intervention, deblinding on demand after 12 weeks was allowed to provide other treatment options outside the   trial   instead of   suffering   for 12   months.  These patients left the trial with the worst outcome, which was carried forward. All these “worst” data were carried for- ward and used for analysis.

 

Figure 1. Flow of participants through the study.

aSafety population: all patients receiving at least one treatment session.

bITT population, intent-to-treat. All patients who had at least one treatment session and also at least one evaluation after the first treatment without severe deviation of entry criteria “full analysis set,” according to ICH E9 Biostatistics.11,12

cPP population, per protocol. Exclusion of patients from ITT population with protocol violations (inclusion/exclusion criteria, incomplete study treatment, premature discontinuation).

dSufficient response was considered at least a 60% reduction in pain on 2 of the 3 VAS scales (overall success VAS), or if less pain reduction, then the patient had to be able to work and complete activities of daily living, had to be satisfied with the outcome of the treatment, and must not have required any other treatment to control heel pain. Participants were requested to continue until follow-up 2 (12 months).

eData reflects last value carried forward (LVCF) replacement of missing values of “nonresponders” in the ITT population.

 

 

 

maximum tenderness over  the  medial tubercle of the  calcaneus.1,4  To be eligible, participants had  to score  significant  pain of at  least 5  or  greater on  all 3  visual  analog scale  (VAS) scores  (with a maximum of 10), must have  had significant  limitation on  the  Roles  and   Maudsley  Score (fair or poor), and  had  to have  failed results from at least 2 non pharmacological and 2 pharmacological treatments. All patients had to respect   a sufficient washout period after each intervention prior to enrollment. The  specific washout phases were  determined as  at least 6 weeks from  last corticosteroid injection; 4 weeks from  the last local  anesthetic injection, iontophoresis, ultrasound, and  electrotherapy; 1 week  from  the  last intake of no steroidal antiinflamma-tory  drugs (NSAIDs); and  2 days from  last heat,  ice, mas- sage,  stretching, or modification of night splinting and orthotics.

 

Exclusion Criteria

 

Reasons for exclusion are listed in the Appendix B (avail- able online at http://ajs.sagepub.com/supplemental/). Major reasons for exclusion were rheumatic or other systemic inflammatory disease, osteomyelitis, active infection or his- tory of chronic infection in the treatment area, neurological or vascular insufficiencies, nerve entrapment syndrome, disturbance of coagulation or ongoing anticoagulatory therapy, significant bilateral heel pain in need of medical treatment, and pregnancy.

 

Study Procedures

 

Randomization and treatment were started within 28 days after   screening. Radial ESWT or identical placebo   were administered in 3 sessions, each 2 weeks (±4 days) apart. A total   of  2000   shock  waves  of  the  assigned  intervention were  delivered per session with the Swiss Doloclast radial shock wave  device  (EMS  Electro Medical Systems, Nyon, Switzerland).  Before the  intervention, the  point  of maxi- mum  tenderness was  clinically located  by the  treating clinician, and  the  hand-piece was  coupled   to  the  identified area  by   using   specific  ultrasound   coupling  gel  (EMS Electro Medical Systems).

In the  treatment group, 2000  impulses of radial shock waves with an  energy flux density of 0.16  mJ/mm2  and  a rate  of 8 impulses per  second  were  applied at  each  treatment  session. Patients in the control group received identical placebo intervention with a placebo hand-piece that prevented transmission of shock waves. The  placebo  hand- piece  was  identical in  design, shape, and  weight to ensure that  there  was  no way  to identify the  placebo  hand-piece. The   treatment in the placebo   group   was the same   com- pared with the active one. Thereby, set up and sound created by the shock wave device was identical in both groups; how- ever, no energy was   administered in the   placebo group. The  intervention was  performed in  the  office  by  the  non- blinded  orthopedic  surgeon  or  podiatrist,  locating  the tip  of  the   applicator  to  the   most   tender  point  at   the medial calcaneal tubercle, controlling proper  placement by patient-controlled  feedback,  and   adjusted  during  treatment  if necessary.

 

A standardized rescue medication was allowed through- out the entire study if pain became unbearable (2 g of acetaminophen per   day   for   up   to   14   days after    the   last intervention; thereafter, 2 g of acetaminophen per week). No other therapies were allowed, and orthotics could not be modified until the 12-week follow-up (follow-up 1).

 

Outcome Measures

 

The  primary outcome measure was  overall heel pain reduction measured by  the  percentage change of the  VAS composite score  12  weeks after  treatment compared with baseline, with last value carried forward (LVCF) replacement  of missing values with the  last recorded  value and correction for interfering analgesic therapy. The  12-month analysis was  performed in  the  same  manner by  replacing missing  values  in   LVCF and   correction  for   interfering analgesic  therapies  with  the   last  recorded    value. The heel pain composite score was defined as the sum of three 10-cm  VAS scores:  heel  pain when  taking the first steps  in the  morning, heel  pain while doing   daily  activities, and heel   pain  while applying  a  standardized  local   pressure with the  Dolor meter (EMS  Electro  Medical Systems)  to quantify local  pressure pain. The  Dolor meter is  a  device that  allows for objectivity of pressure application, with an integrated  scale   to  exactly  determine the   applied  local pressure.17  The  blinded investigator used  the  Dolor meter to measure pressure sensitivity  at  the  point  of maximum tenderness. The pressure level measured at the Dolor meter scale   that   just   elicited unbearable pain was documented as baseline value and was quantified by the Dolor meter on the 10-cm VAS scale. At each follow-up visit, the same Dolor meter pressure was applied, and the subject was   asked to score the pain on the VAS. The   increased pressure pain tolerance reflects the shock wave–induced effect.

The  further primary efficacy criteria were the single success  rates and  the overall success rate  with regard to heel pain, defined as  percentage  decrease of heel  pain larger than 60%  from  baseline at 12 weeks after  treatment for at least 2 of the 3 heel pain (VAS)  measurements. To keep the multiple level of α, the further set of primary efficacy criteria were tested in the a priori–ordered sequence according to the principle of a priori–ordered hypotheses.25

The primary endpoint for comparison of groups was 12 weeks after the last treatment. At  this point  the  decision was  also  made  whether the  patient had  sufficient treatment  response to continue the  study. Sufficient response was considered a minimum 60% reduction in pain on 2 of 3 VAS scores.  Patients who showed sufficient and clinically relevant response to rESWT were to continue in the follow- up 2 period (12 months after last rESWT).  Patients who suffered from  significant pain after  intervention deblinding on  demand  after 12 weeks  were  allowed  to  explore other  treatment options outside the trial instead of suffer- ing  for  12  months. These patients left the trial with the worst outcome, the data of which were carried forward and used for analysis.

Secondary outcome measures were changes in Roles and Maudsley score,   SF-36 physical percent changes, SF-36 Mental percent changes, investigator’s judgment of effectiveness (7-point scale), patient’s judgment of therapy satisfaction (7-point scale), and   patient recommendation of therapy to a friend (all at   12   weeks after   treatment). Furthermore, VAS composite score, success rates, and single VAS scores were assessed after completion of follow-up 2 (12 months after last treatment session).

 

Safety Criteria

 

All patients who had at least one treatment session were analyzed for safety. Patients were followed throughout the study, and all local tissue effects and adverse events were recorded. Additionally,  the  investigator’s global judgment of  tolerability was  assessed on  a  7-point rating  scale   12 weeks  after   the  last  treatment. To assess local   adverse event    tendon    rupture   observation, Semmes-Weinstein5.07 (10 g) Monofilament Assessment, Toe Clawing Observation, and Ankle-Brachial Assessment of the lower extremity were performed at each visit. All assessments but one were done by clinical examination. The Semmes- Weinstein Monofilament was used to assess global neurological deficiencies. A   10-gram (5.07   log)   monofilament wire was applied to each foot at 10 sites. Loss of protective sensation generally is indicated by a patient’s inability to feel the monofilament at 4 or more of the 10 sites.

 

Statistical Analysis

 

The study had a statistical power of 90% to detect a reduction by 50 percentage points in the primary outcome measure of a reduction of VAS composite score from baseline to

12 weeks after completion of shock wave   treatment. A dropout   rate of 10% was calculated as well before study start.

To keep  the  multiple level  of α,  the  set  of primary efficacy criteria were  tested  in  the  a priori–ordered  sequence according to Maurer.25 By this, if  the  first test  is  statistically  significant  (VAS  composite score),   the  second   test (overall success rate)  can be performed to confirm with full level  of α.  If the  second  test  (overall success rate)  is  also statistically  significant, the  single  success rates  can   be tested   to  confirm with full  α  in  the  sequence   “heel  pain when  taking first steps  of the  day,”  “heel  pain while doing daily activities,” “heel pain after application of the Dolor meter” as  long  as  the  preceding test  is  statistically significant. Efficacy of the rESWT treatment is proved if at least the first hypothesis (VAS composite score) shows   a statistically significant result. A value of P < .025 (1-sided) was considered statistically significant.

To identify differences in  effect  size  between  the  different   intervention  groups,  the   Mann-Whitney  effect   size with predefined benchmarks was  used  to define  the probability  that    a   randomly   selected   participant   from  the rESWT group  was  better  off than a randomly selected  participant from the control  group. In accordance with Colditz et  al,6  the  authors used  relevant benchmarks that  corresponded  to a Mann-Whitney effect  size  of 0.5  for equality (active therapy no  better  or  worse  than placebo);  0.44  or

0.56 for small-sized inferiority or superiority, respectively;

size demonstrated more than small superiority of rESWT for all 5 a priori–ordered hypotheses compared with placebo (Mann-Whitney effect size >0.56), demonstrating significant as well as clinically relevant effects.
Regarding follow-up 2 (12 months after rESWT) the P values of all 5 primary efficacy criteria were far below the predefined level of significance (.025, 1-sided, exploratory interpretation, Table 2). Nonresponders of follow-up 1 period and premature discontinuations were included by
LVCF replacement of missing values and for safety analysis.
These results even demonstrated a pronounced treatment effect at follow-up 2, and treatment success was maintained. The composite VAS score of the heel pain was –84.8% in the patients treated actively and –43.2% in the placebo group (P < .025). Thus, there is strong evidence for long-term superiority of the ESWT treatment compared with identical placebo.
To assess the stability of the results, different sensitivity analyses were performed for the primary efficacy criteria at follow-up 1 and 2 assessing a per-protocol analysis, a supportive analysis for the ITT data set without any correction for interfering analgesic therapy, a further supportive
sensitivity analysis for the ITT data set with correction for interfering analgesic therapy by means of the worst rank score technique, and an analysis of the data set with the “data as available” instead of LVCF replacement of missing values. All in all, the results of the sensitivity
analyses support the results of the confirmatory analysis (see Appendix D for details, available online at http://ajs.sagepub.com/supplemental/).
Secondary Outcome Measures The efficacy results demonstrated superiority of the rESWT group not only in the confirmatory analyses, but also in the supportive sensitivity analyses and in the analysis of the secondary outcome measures. All tested secondary efficacy criteria,
including the SF-36 score, the Roles and Maudsley Score, global judgment of effectiveness, therapy satisfaction, and therapy recommendation, showed better outcome at the primary endpoint in favor of the rESWT group, and all test results were statistically significant (P < .025 1-sided).
Furthermore, all Mann-Whitney effect sizes denoted more than small superiority of the rESWT group compared with placebo (Table 3). Thus, there is evidence for benefit of patients with painful heel by rESWT treatment not only through reduced pain but also by generally improved wellbeing.
The positive result was also reflected by the high recommendation rate of participants with rESWT treatment with a final recommendation of study therapy in 91.2% of the rESWT group compared to 69.1% of the participants with placebo intervention.
Adverse Events and Safety Criteria A total of 251 subjects received at least one treatment session (“safety population”; Figure 1). There were 50 devicerelated adverse events in 33 patients of the rESWT group and 11 adverse events in 10 subjects in the placebo group.
A total of 46 of 50 device-related nonserious adverse events in the ESWT group was due to pain and discomfort during treatment as displayed in Figure 2. The duration of discomfort was reported as maximal 10 minutes mostly, and no participant requested local anesthesia during rESWT, even though this was offered to all patients. Device-related adverse events had no influence on outcome. No adverse or severe adverse event occurred regarding tendon rupture observation, Semmes-Weinstein 5.07 (10 g) Monofilament Assessment, Toe Clawing Observation, and Ankle-Brachial Assessment.
At the primary endpoint 12 weeks after the last treatment, the tolerability of the treatment was judged by the investigator as “very good” or “good” in 93.8% of the rESWT subjects and in 90.1% of the placebo group.
DISCUSSION
The present placebo-controlled study was conducted to investigate the safety and effectiveness of rESWT in the treatment of recalcitrant plantar fasciitis. Plantar fasciitis is a common complaint and can be especially disabling in 

1,4,29,31athletes.Goals of treatment are pain relief and restoration of function. Martin et al 24 and Crawford and 8 Thomson reviewed numerous studies of nonsurgical treatment for plantar fasciitis such as stretching, cryotherapy, heel cushions and shoe inserts, night splints, custom-made orthotics, anti-inflammatory drugs, corticosteroid injection, and immobilization and showed success rates ranging from 44% to 90%.1,4,8,24Nevertheless, not more than limited evidence of efficacy could be demonstrated.
4,8 For patients with chronic heel pain resistant to nonsurgical treatment, surgical interventions are suggested. Surgery, however, can be associated with prolonged healing 8,9 and did not prove superior to ESWT.
9,38 Extracorporeal shock wave therapy for plantar fasciitis has been investigated in multiple well-designed, randomized, and placebo-controlled trials, providing evidence of effectiveness and safety of treatment. 17,23,27,29,30,31,33 These studies also demonstrated significant influence of treatment regimen and concomitant anesthesia on outcome.
19,30 Notably, some double-blind randomized, controlled trials that failed to show the superiority of ESWT over placebo focused the acoustic energy at anatomical landmarks rather than at the point of greatest tenderness as defined by the participant, and local anesthesia was used in some of the investigations in an effort to blind the participants.
5,18,32Recent studies have demonstrated that localanesthesia may inhibit direct analgesic effects like themodification of the release of pain mediators, hyperstimulation,and the gate-control mechanism.
18,21,22,28,37Theseobservations were further supported by a study by Rompeet al 30demonstrating ESWT applied without local anesthesia to be significantly more effective than ESWT used with local anesthesia.
Compared with focused shock wave applicators, rESWT devices address larger treatment areas, thus providing potential advantages in superficial applications like tendinopathies and skin conditions.
7,15,16,28 For deep soft tissue treatments or bone injuries, the radial technique has some limitations regarding penetration depth and higher energy levels.
7,15,16In contrast to so-called focused shock wave therapies, the radial technique is used to treat the painful region rather than a painful point. It is well known that heel pain originates from a painful area along the plantar fascia rather than a certain locally limited spot. From the technical point of view, radial shock wave therapy addresses more the area of pathologic changes compared with focused devices.
10,15,22,30 Due to the patient controlled application and the missing need to control the 

Figure 2.    A, device-related adverse events in the radial extracorporeal shock wave therapy group. B, device-related adverse events in the placebo group.

focus zone, radial shock wave therapy seems to be easier to apply. 15,20 Because treatment regimen and shock wave parameters have significant influence on outcome, pooling of data in systematic reviews and meta-analyses is critical, and effectiveness has to be assessed for the different devices and treatment protocols. Buchbinder 5,17,27,32,33,35 5 et al 18 and Haake et al used local anesthesia or nerve blocks and found no difference. When no local anesthesia 
 

was   used,   Gollwitzer et  al,17   Rompe et  al,30  and   Malay et al23 found  significantly better  outcome  after  shock wave treatment. In the present study, radial shock waves were oriented without anesthesia by patient-guided feedback to the point of maximum tenderness.

The present randomized, placebo-controlled study demonstrated significant improvement of pain scales and functional measurements, as well as quality of life, after rESWT at follow-up compared to baseline. Furthermore, rESWT proved superior to placebo with regard to the primary outcome measures of “changes in VAS composite score of heel pain” and “overall success rate” at 12 weeks and all secondary outcome measures at 12 months after intervention. At the time of follow-up 1, the VAS composite score was reduced by 72.1% in the rESWT group compared with 44.7% in the placebo group, which was statistically significant.  Furthermore, the between-group difference of nearly 30%  is considered  clinically  relevant.13 The superiority  of rESWT compared with placebo was  not only limited to the primary criterion of effectiveness but also strongly sup- ported by the results of the outcome  measures’ overall success   rate,  success  rate  of  heel  pain  while  doing  daily activities, success rate of heel pain after the  application of the  Dolor meter, Roles and  Maudsley score, percentage changes  from baseline  of  the  SF-36  summary measures mental  and   physical  health, investigator’s  and   patient’s judgment of effectiveness, and  the  patient’s rate of recommendation of the applied therapy to a friend. An additional assessment of the Mann-Whitney effect size revealed more than small superiority of rESWT in all determined criteria both at 12 weeks and at 12 months after the intervention. Furthermore,  several sensitivity  analyses were performed to  check  the  stability of  the  data, which all  corroborate effectiveness of rESWT compared with placebo showing significant superiority  (see  Appendix  D,  available  online at http://ajs.sagepub.com/ supplemental/).

Regarding the second follow-up at 12 months after  shock wave   treatment,  superiority  of  rESWT   compared with placebo  was  even more pronounced, with a reduction of the VAS  composite score  from  baseline of  84.8% after   shock wave   treatment  compared  with   43.2%  in   the   placebo group, demonstrating a more than 40%  between-group difference.  All other  outcome  measures also  showed  superiority  of the  rESWT  group, thus proving excellent long-term efficacy and  supporting the  application of rESWT in  the treatment of chronic plantar fasciitis. Apart from  the investigated pain scales, we were  able  to demonstrate significant  improvement in  the  scores  evaluating quality of life  (SF-36) and  function (Roles and  Maudsley score). Thus, there is evidence for benefit of patients with painful heel by ESWT treatment not only   through reduced pain but also by generally improved well-being.

Treatment was   applied without anesthesia, and   our results demonstrated rESWT to be safe with excellent tolerability. The  results demonstrate that  patients assigned the  rESWT were  found  to  have   more  pain during treat- ment  compared with placebo  but no one required any  local anesthetic. The   sensitivity analysis demonstrates no differences in outcome with regard to all side effects.

From the clinical point of view the outcome regarding recommendation and   global judgment by patients and investigators demonstrated high clinical impact and acceptance. Notably, nearly 70% of patients of the placebo group would also recommend the received treatment to a friend. This  large placebo   effect  demonstrates the  effectiveness of the blinding technique, which also  was  found  in other  randomized, controlled studies.17,23,35  In review, with a mean  improvement of the  VAS composite score  of more than 40%  in  the placebo  group  at follow-up compared with baseline, the  power  of the  placebo  effect  in  these  kinds of studies becomes  obvious and  has  to be addressed by  randomized, placebo-controlled studies  to  analyze the  pure placebo  effect.  The   associated placebo  effect  is  related  to the  device  itself but  also  to the  procedure and  the  physician.26,34,36 The  pure  treatment effect and the associated so- called placebo  effect are  not distinguishable and  clinically used  together.26,34,36

Radial ESWT   demonstrated safety and   effectiveness with a protocol of 3 consecutive treatments (3 × 2000 impulses, 0.16 mJ/mm2), applied without anesthesia to the spot of greatest tenderness. Radial ESWT can be strongly recommended for patients with therapy-resistant plantar painful heel syndrome. Especially  in  the  cases   of  failed nonsurgical treatment, rESWT   represents an   excellent alternative to surgery because  anesthesia is  not  required and  long  recovery times are  avoided. In addition, partici- pants were not required to refrain from any sports activities during the course of the study. Furthermore, rESWT represents  an   effective treatment  modality  that   can   be administered on an  outpatient basis.

ACKNOWLEDGMENT

 

The   study was supported by   Electro Medical Systems, Nyon, Switzerland. The sponsor of the study did not have any influence on data collection, analysis, or publication. No constraints were placed on publication of the data.

 

 

REFERENCES

 

1. ACFAS Clinical Practice Guideline Heel Pain Panel. The diagnosis and treatment of heel pain. J Foot Ankle Surg. 2001;40:329-340.
2. 2. Atkins D, Crawford F, Edwards J, Lambert M. A systematic review of treatments for the painful heel. Rheumatology (Oxford). 1999;38:968-973.
3. 3. Buch M, Knorr U, Fleming L, et al. Extracorporeal shockwave therapy in symptomatic heel spurs: an overview. Orthopade. 2002;31:637-644.
4. Buchbinder R. Clinical practice.  Plantar  fasciitis.  N  Engl J  Med.

2004;350:2159-2166.

5. 5. Buchbinder R, Ptasznik R, Gordon J, Buchanan J, Prabaharan V, Forbes A. Ultrasound-guided extracorporeal shock wave therapy for plantar fasciitis: a randomized, controlled trial. JAMA. 2002;288:1364-1372.
6. Colditz GA, Miller JN, Mosteller F. Measuring gain in the evaluation of medical technology: the probability of a better outcome. Int J Technol Assess Health Care. 1988;4:637-642.
7. Coleman AJ, Choi MJ, Saunders JE. Theoretical predictions of the acoustic pressure generated by a shock wave lithotripter. Ultrasound Med Biol. 1991;17:245-255.
8. Crawford F, Thomson C. Interventions for treating plantar heel pain.

Cochrane Database Syst Rev. 2003;CD000416.

9. Davies MS, Weiss GA, Saxby TS. Plantar fasciitis: how successful is surgical intervention? Foot Ankle Int. 1999;20:803-807.
10. Eisenmenger W, Du XX, Tang C, et al. The first clinical results of

“wide-focus  and  low-pressure”  ESWL.  Ultrasound  Med  Biol.

2002;28:769-774.

11. 11. European Medicines Agency. ICH Topic E6, Guideline for Good Clinical Practice. http://www.emea.europa.eu/pdfs/human/ich/013595en.pdf. Published July 2002; accessed August 14, 2008.
12. 12. European Medicines Agency. ICH Topic E9, Statistical Principles for

Clinical  Trials.  http://www.emea.europa.eu/pdfs/human/ich/036396en

.pdf. Published September 1998; accessed August 14, 2008.

13. Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11- point numerical pain rating scale. Pain. 2001;94:149-158.
14. Furia JP. The safety and efficacy of high-energy extracorporeal shock wave therapy in active, moderately active, and sedentary patients with chronic plantar fasciitis. Orthopedics. 2005;28:685-692.
15. Gerdesmeyer L, Maier M, Haake M, Schmitz C. Physical-technical principles of extracorporeal shockwave therapy (ESWT). Orthopade.

2002;31:610-617.

16. 16. Gerdesmeyer L, Schrabler S, Mittelmeier W, Rechl H. Tissue-induced changes of the extracorporeal shockwave. Orthopade. 2002;31:618-622.
17. 17. Gollwitzer H, Diehl  P,  von  Korff  A,  Rahlfs  VW,  Gerdesmeyer  L.

Extracorporeal shock wave therapy for chronic painful heel syndrome: a prospective, double-blind, randomized trial assessing the efficacy of a new electromagnetic  shock  wave device. J Foot Ankle Surg. 2007;

46:348-357.

18. Haake M, Buch M, Schoellner C, et al. Extracorporeal shock wave therapy for plantar fasciitis: randomised, controlled, multicentre trial. BMJ. 2003;327:75.
19. Labek G, Auersperg V, Ziernhold M, Poulios N, Bohler N. Influence of local anesthesia and energy level on the clinical outcome of extracor- poreal shock wave-treatment of chronic plantar fasciitis. Z Orthop Ihre Grenzgeb. 2005;143:240-246.
20. Magosch P, Lichtenberg S, Habermeyer P. Radial shock wave therapy in calcifying tendinitis of  the rotator  cuff—a  prospective  study.  Z Orthop Ihre Grenzgeb. 2003;141:629-636.
21. Maier M, Averbeck B, Milz S, Refior HJ, Schmitz C. Substance P and prostaglandin E2 release after shock wave application to the rabbit femur. Clin Orthop Relat Res. 2003;406:237-245.
22. Maier M, Milz S, Wirtz DC, Rompe JD, Schmitz C. Basic research of applying extracorporeal shockwaves on the musculoskeletal system: an assessment of current status. Orthopade. 2002;31:667-677.
23. 23. Malay DS, Pressman MM, Assili A, et al. Extracorporeal shockwave therapy versus placebo for the treatment of chronic proximal plantar fasciitis: results of a randomized, placebo-controlled, double- blinded, multicenter,   intervention   trial.   J   Foot   Ankle   Surg.

2006;45:196-210.

24. Martin RL, Irrgang JJ, Conti SF. Outcome study of subjects with inser- tional plantar fasciitis. Foot Ankle Int. 1998;19:803-811.

 

25. Maurer W, Hothorn LA, Lehmacher W. Multiple comparisons in drug clinical trials and preclinical assays: a priori–ordered hypotheses. In: Vollmar J, ed. Testing Principles  in  Clinical and Preclinical Trials. Stuttgart, Germany: Gustav Fischer; 1995:3-18.
26. Moseley JB, O’Malley K, Petersen NJ, et al. A controlled trial of arthroscopic  surgery for osteoarthritis of the knee. N Engl J Med.

2002;347:81-88.

27. 27. Ogden JA. Extracorporeal shock wave therapy for plantar fasciitis: ran- domised, controlled, multicentre trial. Br J Sports Med. 2004;38:382.
28. Rompe JD, Buch M, Gerdesmeyer L, Haake M, Loew M, Maier M, Heine J. Musculoskeletal shock wave therapy—current database of clinical research. Z Orthop Ihre Grenzgeb. 2002;140:267-274.
29. 29. Rompe JD, Decking J, Schoellner C, Nafe B. Shock wave application for chronic plantar fasciitis in running athletes: a prospective, randomized, placebo-controlled trial. Am J Sports Med. 2003;31:268-275.
30. Rompe JD, Meurer A, Nafe B, Hofmann A, Gerdesmeyer L. Repetitive low-energy shock wave application without local anesthesia is more efficient than repetitive low-energy shock wave application with local anesthesia in the treatment of chronic plantar fasciitis. J Orthop Res.

2005;23:931-941.

31. Rompe JD, Nafe B, Furia JP, Maffulli N. Eccentric loading, shock- wave treatment, or a wait-and-see policy for tendinopathy of the main body of tendo achillis: a randomized, controlled trial. Am J Sports Med. 2007;35:374-383.
32. Speed CA, Nichols D, Wies J, Humphreys H, Richards C, Burnet S, Hazleman BL. Extracorporeal shock wave therapy for plantar fasciitis: a double-blind,  randomized,   controlled   trial.   J   Orthop   Res.

2003;21:937-940.

33. Theodore GH, Buch M, Amendola  A, Bachmann  C,  Fleming LL, Zingas C. Extracorporeal shock wave therapy for the treatment of plantar fasciitis. Foot Ankle Int. 2004;25:290-297.
34. Thomas JR. Placebo surgery. Mo Med. 1999;96:41.
35. Thomson CE, Crawford F, Murray GD. The effectiveness of extra cor- poreal shock wave therapy for plantar heel pain: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2005;6:19.
36. Tjomsland O, Ekeberg O, Saatvedt K. Placebo effect in research related to surgery and technical procedures [in Norwegian]. Tidsskr Nor Laegeforen. 2001;121:2290-2293.
37. Wang CJ, Huang HY, Pai CH. Shock wave-enhanced neovasculariza- tion at the tendon-bone junction: an experiment in dogs. J Foot Ankle Surg. 2002;41:16-22.

38. Weil LS Jr, Roukis TS, Weil LS, Borrelli AH. Extracorporeal shock wave therapy for the treatment of chronic plantar fasciitis: indications, protocol,  intermediate results, and a comparison  of results to fas- ciotomy. J Foot Ankle Surg. 2002;41:166-172