1

Trial of two different ESWT energy flux density levels for the treatment of

chronic patellar tendinopathy in an active population.

¹Bruce Twaddle , ²Wayne Hing, ³Kenneth Craig

¹Chief of Orthopaedic Trauma, Auckland Hospital. Department of Orthopaedics Auckland University. Sports

Orthopaedics Consultant, UniSports Medicine. ²Assoc. Professor and Head of Health and Rehabilitation Research

Institute Auckland University of Technology. ³BHSc. Podiatry, Dip. Pharmacology, PG MSK Pain Management

Studies.

Abstract

Background: Patella tendinopathy (PT) is a commonly seen condition where activity related overload of

the knee extensor mechanism is seen to be the primary cause of complaint and disability presenting a

clinical challenge in its management (Taunton, 2003; Warden & Brunker, 2003; Wang et al 2007;

Maffulli et al 2010). Despite the abundance of therapeutic options available to treat tendinopathies, the

inconsistencies, irregularities and the lack of evidence based guidelines for treating this condition (Frohm,

2006; Crossley et al 2007; Andres & Murrell, 2008; Maffulli & Longo, 2008), warrants the exploration of

a treatment modality that may help address this issue, especially in unresponsive chronic conditions.

Aim: The aim of this study is to determine if medium and high energy extracorporeal shockwaves are

effective in treating chronic patella tendinopathy versus placebo in an active population that has failed to

respond to two or more non-surgical treatment methods.

Design: Randomised double blind placebo controlled trial.

Method: 108 patients randomized equally into three groups; two treatment groups and one placebo.

Patients with clinically diagnosed chronic patella tendinopathy with a minimum disability period of 4

months who have all failed three other treatments including eccentric exercises will be referred via a

network of physiotherapist, sports physicians and orthopaedic surgeons. Baseline scores using Visual

analogue scale (VAS), Victoria Institute of Sports Assessment – Patella (VISA – P), ultrasonography,

vertical jump test (VJT), and single leg decline (SLD) will be conducted and reassessed post treatment.

One treatment group will receive a single session of high energy ESWT and the other treatment group

will receive a single session of medium energy ESWT. Control group will receive 3000 blocked impulses

(placebo). Treatments will be conducted without the use of local anesthesia or pain medication.

2

Treatment objective: To determine if medium or high energy ESWT will demonstrate a superior

outcome for treatment of patients with chronic patellar tendinopathy versus placebo. A minimum of a 15

point increase from baseline VISA - P scores will be considered a positive outcome. Other markers such

as non-dependence on pharmacogenics for increased function, VJT and SLD will be correlated with the

VISA – P scores to provide for a more accurate final descriptive of trial outcomes.

Discussion: There seems to be a dearth of quality evidence for the treatment of patella tendinopathy

despite the abundance of treatment options available to practitioners. The use of ESWT has been seen to

be effective for the treatment of chronic plantar fasciitis and Achilles tendinopathy in several studies

(Ogden et al 2002; Carter et al 2004; Ogden et al, 2004; Furia, 2006, 2008; Wang et al 2006), as well as

from our own clinical experience, suggesting that similar outcomes may be plausible when using ESWT

for chronic patella tendinopathy. While there have been some dated and recent studies investigating the

efficacy of ESWT for patella tendinopathy there is still debate as to which type of energy levels should be

utilized. Our study hopes to answer the question: Is ESWT an effective treatment for the treatment of

chronic patella tendinopathy? While comparing two different energy levels (medium and high energy), in

a placebo controlled trial. To our knowledge this will be the first study to undertake the comparison of

both medium and high energy ESWT in a placebo controlled study for patellar tendinopathy.

Trial registration No: LRS/11/02/004

Keywords: patellar tendinitis, patellar tendinopathy, tendinopathy, patellar injury, treatment for

tendinopathy, inflammation in tendinopathy, eccentric exercises, cortisone injection for tendinopathy, NSAID’s, extracorporeal shockwave therapy, aging and tendons, overuse sports injury, injury in elite

athletes.

Corresponding authors:

Twaddle, B.

71 Merton Road,

St. Johns, Auckland,

New Zealand

jan@sportsmed.net.nz

Hing, W.

Auckland University of Technology

90 Akoranga Drive, North Shore City,

New Zealand

wayne.hing@aut.ac.nz

Craig, K.

Level 2, 626 Great South Road,

Ellerslie, Auckland,

New Zealand

nopain@xtra.co.nz

3

Introduction

Tendinopathy is a generically used term that encompasses pain and discomfort occurring around

tendons as a result of repetitive or overuse syndromes due to sports, as well as activities of daily

living. Patella tendinopathy (PT) is a commonly seen insertional tendinopathy affecting the

physically active where activity related repetitive overload of the knee extensor mechanism is

seen to be the primary cause of complaint and disability presenting a clinical challenge for its

management (Taunton, 2003; Warden & Brunker, 2003; Wang et al 2007; Maffulli et al 2010).

Despite the clinical frequency, there are many unanswered questions and conflicting opinions as

to the etiology, pathophysiology, pain mechanisms and treatment protocols for this condition

(Fredberg & Stengaard-Pederson, 2008). Historically labeled as tendinitis, this condition which

commonly affects the posterior proximal insertion of the tendon at the inferior pole of the patella

displays a degenerative histological pattern devoid of an overt inflammatory process (Alfredson

et al 2001; Hamilton & Purdam, 2004; Wilson & Best, 2005; 2006; Lian, 2005; Magra, 2006;

Crossley et al 2007; Frohm, 2006; Maffulli et al, 2010). Although greater prevalence is seen

among volleyball and basketball players, it affects athletes and enthusiasts over a wider range of

sporting activities and is also known to occur in patients with a sedentary lifestyle (Crossley et al

2007; Lian, 2005; Maffulli et al 2010).

Clinical symptoms

Clinical symptoms may range from mild to disabling with consistent symptomatic findings

commonly presenting as focal tenderness at the inferior pole upon palpation with knee in

extension, with some patients complaining of increased stiffness around the knees in the

mornings (Warden, 2003; Hamilton, 2004; Cook et al 2005; Frohm, 2006). Pain is often

insidious with increasing intensity and frequency that may ultimately interfere with activity and

performance. Other complaints include discomfort when ascending and descending stairs, with

long periods of sitting, and sleep disruption (Warden, 2003). Patients with chronic PT often

present with some or all of the above symptoms, and at times may present with noticeable

wasting of the vastus medialis obliqus muscle with or without reduced thigh circumference and

gastrocnemius atrophy (Cook et al, 2000; Pfirrmann et al 2008).

4

Etiology

The exact etiology of patellar tendinopathy is unclear however multifactorial theories such as

tensile overload, tenocyte related collagen synthesis disruption, tendon load induced ischemia,

neural sprouting, and histological adaptive compressive responses are seen to be some of the

causative factors that give rise to pain, activity disruption and disability in the active and athletic

populations (Cook, 2000; Purdam, 2003; Warden, 2003; Hamilton, 2004; Cook et al 2005; Lian,

2005; 2006; Crossley et al 2007; Frohm, Maffulli, 2008; Maffulli et al 2010). The most

commonly accepted cause for this condition however is seen to be an overuse syndrome of the

knee joint extensor mechanism in combination with intrinsic and extrinsic factors that lead to the

progressive interference or failing of the healing response ( Cook, 2000; Witvrouw et al 2001;

Richards et al 2002; Purdam, 2003; Warden, 2003; Hamilton, 2004; Cook et al 2005; Lian, 2005;

Lian, 2006; Frohm, 2006; Crossley et al 2007; Woodley et al 2007; Maffulli, 2008; Maffulli et al

2010). Chronic patellar tendinopathy as described by Kuttenen et al; is a condition where

symptoms persist for over three months and as more recently described; is devoid of

prostaglandin mediated inflammation (Alfredson et al 2001). This suggests the term tendinitis

may be a misnomer when addressing this condition, and some of the traditional treatment

modalities aimed at inflammatory control such as non-steroidal anti-inflammatory drugs

(NSAID’s) and cortisone injections may not be the most suitable options when treating this

condition especially in chronic states (Wilson 2005; Andres & Murrell, 2008; Maffulli et al

2010). However consideration must be given to the fact that although prostaglandin related

inflammation in chronic tendinopathy may be questioned, neurogenic inflammation due to

increased expressions of neurotransmitters have the potential to initiate peritendinitis, which in

turn may lead to degenerative changes in the tendon (Hart et al 1998; Sullo et al 2001; Fredberg

& Stengaard-Pederson, 2008), hence not totally eliminating the role of inflammation in

tendinopathies further emphasizing the complexity of this condition.

Tendinopathic Pain

With the exception of those with a congenial insensitivity to pain, the experience of pain is

something that humans are familiar with (Ebrahimi-Nejad, 2007; Quniter, 2008), yet this

familiarity with pain has not allowed us to fully grasp the very nature and causative factors of

pain in chronic states (Craig, 2010), as in the case of patellar tendinopathy. Traditionally it was

thought that chronic inflammation was the cause of pain in chronic overuse tendinopathies

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however histological findings indicate the absence of inflammatory mediated markers in

tendinopathy (Kannus & Jozsa, 1991; Astrom & Rausing, 1995; Alfredson et al 1999; Alfredson

& Lorentson, 2002(a); Alfresdon et al 2002; Fredberg & Stengaard-Pederson, 2008) and as such

pain in chronic tendinopathy may originate from a combination of biochemical and mechanical

factors (Khan et al 1999; Khan et al 2002; Sharma & Maffulli, 2005). Pain in tendinopathy may

be multifactorial and is seen to be caused by chemical and neurotransmitter substances as studies

on patients with chronic Achilles and patellar tendinopaties show an increase in levels of lactate,

glutamate, substance P and calcitonin gene related peptide (CGRP) in symptomatic groups

compared to control devoid of pro-inflammatory substances (Alfredson, 1999; Alfredson et al

2002; Sharma & Maffulli, 2005; Alfredson, 2006). Neuromodulators and transmitters such as

substance P and CGRP commonly found in unmyelinated sensory fibers have been found in

increased levels in tendinopathic Achilles and patellar tendons, and elbow epicondyles (Ljung,

2004; Sharma, 2005; Alfredson, 2006). As sensory nerves transmit pain to the spinal cord, the

increased levels of neuropeptides seen in tendinopathic condition may provide some insights and

explanation to the pain associated with these conditions (Ljung, 2004). Increased

neovascularization is seen in patellar tendinopathy but the correlation between pain and

neovasuclarization has not been fully established (Lian et al, 2006; Wang et al 2007).

Treatment options

Current conservative and non-surgical treatment options available for the management and

treatment of patellar tendinopathy include: rest, ice, massage therapy, eccentric exercise,

NSAID’s, cortisone, ultrasound therapy, LIPUS, acupuncture, electrotherapy, taping, sclerosing

injections, blood injection, glyceryl trinitrate patches, and (ESWT) extracorporeal shockwave

therapy (Warden, 2003; Visnes et al 2005; Wilson, 2005; Frohm, 2006; Warden et al 2006;

Crossley et al 2007; Murrell, 2007; Visnes & Bahr, 2007; Wang et al 2007; Maffulli, 2008;

Paoloni et al 2009; Maffulli et al 2010). Despite the abundance of therapeutic options available

to treat tendinopaties, the inconsistencies, irregularities and the lack of evidence based guidelines

for treating this condition (Wilson, 2005; Frohm, 2006; Crossley et al 2007; Andres & Murrell

2008; Maffulli & Longo, 2008) warrants the exploration of a treatment modality that may help

address these issues, especially in chronic nonresponsive tendinopathies.

6

Extracorporeal shock wave therapy (ESWT).

Extracorporeal shock waves (ESW) are acoustic pulses that transmit energy from a generator

source, presented as a single positive peak pressure pulse with a rapid peak rise time of up to

100MPa, followed by a pressure decrease within nanoseconds (Chen et al 2004; Mariotto et al

2005; Angehrn, 2008). The use of ESWT in chronic musculoskeletal injuries have demonstrated

that it is a safe and effective treatment for Achilles tendinopathy, plantar heel pain, pseudo

arthrosis, and calcerea shoulder tendinitis (Ogden, 2002; Carter et al 2004; Ogden et al 2004;

Furia, 2006; Furia 2008; Cacchio, et al, 2009; Craig, 2010). Although the exact mechanism of

the impact on human tissue of ESWT is not completely understood, research has shown that dose

dependant ESWT induces progenitor cell expression, stimulation of mesenchymal stem cell

recruitment and regeneration stimulus, endothelial nitric oxide syntheses (eNOS), neural nitric

oxide syntheses (nNOS), neovascularization (increasing regional blood circulation), transforming

growth factor ß1 (TGF ß1) mediation, collagen type I & III uptake, and a cascade of endogenous

biochemical responses including the down regulation of neurogenic inflammatory substances;

promoting physiological healing in tendon, bone and wounds (Wang, 2002; Chen et al 2004;

Mariotto et al 2005; Moretti et al 2009; Notranicola et al 2010;). Use of ESWT for knee injuries

including patellar tendinopathy have been carried out with some promising results (Vara et al,

2000; Peers, 2003; Peers et al, 2003; Taunton, 2003; Vulpiani et al 2007; Wang et al 2007;

Moretti et al 2009). However, a study recently concluded by Zwerver et al (2010) on sixty four

jumping athletes with patellar tendinopathy concluded that results were disappointing. It must be

noted that there were several disparities in this study but it is not within the scope of this paper to

discuss them at this juncture.

Design

A single centre RCT with blinded assessors and participants dived into three groups. Participants

will be divided randomly into treatment groups. (1) Receiving a single session of medium energy

ESWT, (2) receiving a single session of high energy ESWT, and (3) receiving placebo.

Treatments will be run over a two week period, with a post treatment follow-up of up to 24

weeks commencing at week 4. Patient recruitment will be from an independent referral base of

physiotherapist, sports physicians and orthopaedic surgeons. Study design, and treatment

procedure will be explained to the entire study population and an informed consent will be

7

obtained prior to trial commencement. The study geography would revolve between: the ESWT

treatment centre, the research centre of the Auckland University of Technology (AUT), and

independent sports and orthopaedic clinics located in Auckland, New Zealand. The ESWT

provider will not be blinded in this study and will not be involved in the assessment of treatment

outcomes. Outcome assessors, data collectors and participants will be blinded throughout the

study period. To our knowledge this study is the first to investigate simultaneously two different

energy flux density levels using ESWT in a placebo control trial for the treatment of patellar

tendinopathy.

Sample population

108 participants will be recruited from an independent referral network comprising of both

genders engaged in multi-sports disciplines with and age range of 18 – 35 years old. Participants

would have a clinically established condition of patellar tendinopathy confirmed by ultrasound,

and must have failed to respond to a minimum of three other treatment methods including

eccentric exercises. Baseline measurements will be carried out on all selected participants then

randomized into treatment and control groups. It is our objective to obtain sample populations

with a comparatively narrow range of deviation in age, activity and clinical presentations in

order to minimize variables and reduce the potential for α and ß errors in the final analysis

(Rothman, 2010).

Inclusion and exclusion criteria

Inclusion criterion:

Male and female participants from multi-sports disciplines (aged 18 – 35).

Clinically established tendinopathy by an independent referral panel.

Failed minimum of three other on-surgical interventions including eccentric and muscle

strengthening physiotherapy.

Injury history of 4 – 8 months.

VISA – P score of 60 and below.

Ultrasound confirmation of patellar tendinopathy.

8

Exclusion criterion:

All known contraindications to ESWT (ie pregnancy, coagulative disorders, etc.).

Received a cortisone injection within 8 weeks prior to this trial

Previous knee surgery or arthroscopic investigation.

Presence of patellar fracture.

Arthritic condition of the knee.

Injury history of < 4 months

VISA – P score of > 60

Study size

Our study hypothesizes that 80% of the participants in treatment groups should improve by a 15

point difference in VISA – P scale when compared to control. Based on this expectation with a

power of 85%, a placebo factor of 30%, and a potential for dropout rate of 20%, we require 108

participants to be dived equally into 3 groups of 36 participants.

Randomization

Computer generated randomization will be carried out after final selection, briefing and informed

consent. ESWT therapist will be the only person who is not blinded to treatment groups

(Appendix Figure 1). Study will be carried out on an Intention-to-Treat (ITT) basis.

Treatment

ESWT will be conducted at a single location in Auckland by a single experienced therapist to

ensure proper and uniform ESWT application between the groups. A brief explanation of the

treatment will be provided to each participant, where they will be informed that discomfort may

be experienced and that it may vary between individuals. ESWT sessions will be carried out in

the presence of an independent senior year physiotherapy student assigned by the university to

ensure that ESWT is conducted devoid of therapist bias. All treatments will be carried out

without the use of pain medication or local anesthesia. Participants will be seated off a plinth

with knee in unsupported 90˚ flexion. Medical shockwaves will be generated by an

electrohydraulic orthopaedic device, the OrthoSpec (MediSpec Ltd., Germantown, MD). A

single session of 3000 impulses will be applied directly onto the region of interest propagated by

a water medium and coupling gel. Treatment group receiving medium energy ESWT will be

9

given 3000 impulses at energy density flux levels (EDFL) commencing at 0.12mj/mm² and

concluding at 0.22mj/mm². EDFL in group receiving medium energy will be graduated in 250

impulses increments up to 0.20mj/mm², and after 1000 impulses at 0.20mj/mm² EDFL will be

increased to 0.22mj/mm² for 1000 impulses to conclude the session. Patients receiving high

energy ESWT will receive 3000 impulses at EDFL commencing at 0.12mj/mm² and concluding

at 0.28mj/mm². EDFL graduation in this group will be graduated in 200 impulse increments up

to 0.24mj/mm², and after 1000 impulses at 0.24mj/mm² EDFL will be increased to 0.29mj/mm²

for 1000 impulses to conclude the session.

Placebo treatment

Placebo provided by the manufacturer involves a specially designed metal deflector placed inside

the treatment reflector membrane to deflect shockwaves where a non-therapeutic EDFL of below

0.02mj/mm² may be released into the focal region (Medispec, Germantown). Reflector will not

be visible to participants and sound levels during treatment will not be modified by the reflector

ensuring this aspect of uniformity between the treatment groups. Placebo group will receive 3000

impulses ranging from EDFL of 0.12mj/mm² and concluding at 0.24mj/mm², graduated at 250

pulse increments up to 0.20mj/mm², where after 1000 impulses increased to 0.24mj/mm² for

1000 impulses to conclude the session. It is to be noted that these impulses will be blocked by an

internal membrane deflector resulting in a non-therapeutic EDFL onto treatment site.

Concurrent treatment

All forms of anti-inflammatory medication will be ceased throughout the study period (although

analgesics such as paracetamol may be allowed where necessary), and participant will be

restricted to sedentary activity for 6 – 8 weeks. On week 4 graduated eccentric and strengthening

therapies may be introduced without prematurely overloading the recently rehabilitated tendon

and according to patient’s minimum threshold.

Measurement

Baseline measurements will be compared to post intervention scores commencing form week 4

post treatment, and reassessed at weeks; 8, 12 and 24. Patient data will include personal details,

10

demographics, present and past medical history leading up to the study. Adverse events will be

recorded on clinical assessment sheets should they arise.

Visual Analogue Scale (VAS)

Measures subjective activity of daily living scores and post treatment measurements such as the

vertical jump test and single leg decline on a 25˚ decline board (Purdam et al 2003).

VISA – P questionnaire

The VISA – P is a reliable instrument to measure self reported severity and changes specifically

designed for patellar tendinopathy, and has been used by many trials investigating patellar

tendinopathy internationally (Taunton, 2003; Frohm, 2006; Maffulli et al 2009, Zwerver et al

2010).

Ultrasound

The hypo-echogenity, tendon thickness and diameter, presence of neovascularization and calcific

appearance if present will be obtained and monitored by an experienced musculoskeletal

sonographer and remarked by a radiologist at baseline and at week 24. Ultrasound is more

accurate in capturing the fine internal structure and anatomic border of the patellar tendon for

confirming clinical tendinopathy (Karmel et al 2004; Warden et al 2007; Fredberg & Stengaard-

Pederson, 2008). Both sonographer and radiologist will be blinded.

Follow-up

Follow-ups will commence during weeks 4, 8, 12 and 24. Participants will be provided a journal

to record details of their treatment and injury progress on a weekly basis, these entries will be

recorded into patient files by blinded data processors.

Statistical and data analysis

Multilevel analysis will be conducted to weigh the difference between primary and secondary

endpoints of this trial and the independent variables that may occur due to the randomization

process. Further analysis will be conducted to arrive at a truly significant conclusion, where the

confidence intervals (CI) will be calculated based on both size and precision reflected by the P-

value (Rothman, 2010). Changes from baseline scores and their relevance between treatment

11

groups and placebo as well as differentials between each group will be tabulated in a 2x2

contingency table to provide greater truth when providing proof of the treatment outcomes for

this study (Bogduk, 1998). Sample size was calculated based on a power of 85% and a placebo

factor of 30% with an additional 20% dropout rate adjusted into the calculations. Based on the

participant size of each group the comparative calculations of treatment outcomes will be

calculated on a one-on-one basis; High energy vs Medium energy, High energy vs Control, and

Medium energy vs Control. At the conclusion of this study further plans to conduct longer term

follow-ups on treatment group will be planned to determine the survival curves of treatment

outcomes. ITT analysis will be conducted to reduce bias, preserve sample size, and provide for

more accurate data tabulation (Lewis & Machin, 1993; Montori & Guyatt, 2001; Sainani, 2010).

Discussion

Our study intends to investigate the efficacy of ESWT for the treatment of chronic patellar

tendinopathy unresponsive to other non-surgical methods currently used. From our personal

clinical experience of using ESWT, most of our referrals are sent for chronic unresponsive

conditions. This investigative theme and pattern is seen to be consistent when reviewing

literature investigating the use of ESWT in various tendinopathies and musculoskeletal issues.

As such the objective of our investigation using ESWT for patellar tendinopathy is thematic with

our clinical experience and published literature, and does not wish to explore the use of ESWT as

a primary therapy for patellar tendinopathy. Our study has put in place some variable controls in

order to reduce the standard deviation range, such as:

The cessation of steroidal and non-steroidal anti-inflammatory drugs (SAID’s &

NSAID’s) once participants were selected into the study. Some previous studies involving

ESWT did not allow those who were on continuous NSAID’s to participate in the study.

However our study intended to reproduce a real-life clinic situation, and therefore

allowed such participants to be included.

The equal restrictions on training and activity throughout the study period, across the

groups ensures uniformity while recognizing requirements of tendon healing.

12

Clinically diagnosed and established chronic patellar tendinopathy that have failed a

minimum of three other treatment methods. This aspect of our study removes the sole

dependence on the self reporting nature of the VISA – P instrument, reducing the

potential for α and ß errors.

This study uses two different ESWT energy levels and compares them to control; this was to

initiate an investigation that may provide greater premise and insight as to the type of energy

levels that should be selected when considering the use of ESWT for chronic patellar and other

tendinopathies.

Conclusion

Chronic patellar tendionpathy is a complex condition that causes performance disruptions and

disability especially in active populations, with the lack of an evidenced based approach for its

management and containment. When considering treatment options for overuse tendinopathies, a

thorough appreciation of the properties of a healthy tendon and the functional interplay and

mechanical properties of the musculotendon complex is necessary. The proposed mechanisms of

action of ESWT and its safety profile makes it a plausible treatment option when faced with

managing chronic tendinopathies such as patellar tendinopathy. There have been several studies

exploring the use of ESWT on patellar tendinopathy with mixed outcomes. Our study and its

design intend to integrate systemic research with a real-life clinical setting, while seeking to

demonstrate our trail objectives with a strict adherence to medical research standards. This is the

first study to compare different energy density flux levels (EDFL) with a placebo control for the

treatment of patellar tendinopathies and aims to provide some basis to establish which EDFL to

select when considering use of ESWT for this condition.

Authors: KC: Study conceptualization & design, author original manuscript, co-ethics applicant, and ESWT treatment provider. BT: Orthopaedic consultant and clinical assessor. WH: Ultrasonography, ethics applicant and clinical assessor. Conflicting interest:

KC is a Director of Kompass Health Associates,

providers of ESWT services as part of their practice.

13

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Appendix

Participants referred via an independent network of:

Orthopaedic Surgeons

Sports Physicians

Physiotherapists

Control Group (n=36) Treatment Group 2 (n=36) Treatment Group 1 (n=36)

Follow - up Follow - up Follow - up

RANDOMIZATION (n=108)

Lost to Follow-up / discontinued

Analyzed

Lost to Follow-up / discontinued

Analyzed

Conclusion

Analyzed

EXCLUDED

Lost to Follow-up / discontinued

Lost to Follow-up / discontinued

Figure 1. Randomization & Study Flow Chart, including Intention To Treat outline of non-compliant or drop-out groups.