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IMpact of Platelet Rich Plasma OVer Alternative Therapies in Patients with Lateral Epicondylitis (IMPROVE) Protocol for a Multicenter Randomized Controlled Study

Posted Aug 31, 2014 Updated Apr 10, 2023
By Mary M. Chiavaras MD PhD , Jon A. Jacobson MD , Ruth Carlos MD MS , Eugene Maida MD , Todd Bentley MD , Nicole Simunovic MSc , Marilyn Swinton MSc , Mohit Bhari MD PhD FRCSC
13 min read

Introduction

Lateral epicondylitis, commonly known as tennis elbow, is the most common cause of lateral elbow pain and the second most frequently diagnosed musculoskeletal disorder in the neck and upper limb in a primary care setting. Many therapeutic options, including conservative, surgical, and minimally invasive procedures, have been advocated for the treatment of lateral epicondylitis. Although numerous small studies have been performed to assess the efficacy of various treatments, there are conflicting results with no clear consensus on the optimal treatment. In an economic environment with limited health care resources, it is paramount that optimal cost-effective therapies with favorable patient-important outcomes be identified.

Methods and Analysis

This is a protocol paper which outlines a multicenter, multidisciplinary, single-blinded, four-arm randomized controlled trial, comparing platelet-rich plasma (PRP), whole blood injection, dry needle tendon fenestration, and sham injection with physical therapy alone for the treatment of lateral epicondylitis. Patients are screened based on pre-established eligibility criteria and randomized to one of the four study groups using an Internet-based system. The patients are followed at 6-week, 12-week, 24-week, and 52-week time points to assess the primary and secondary outcomes of the study. The primary outcome is pain. Secondary outcomes include health-related quality of life and ultrasound appearance of the common extensor tendon. Two university centers (McMaster University and the University of Michigan) are currently recruiting patients. We have planned a sample size of 100 patients (25 patients per arm) to ensure over 80% power to detect a three-point difference in pain scores at 52 weeks of follow-up.

Ethics and Dissemination

This study has ethics approval from the McMaster University Research Ethics Board (REB# 12-146) and the University of Michigan Institutional Review Board (IRB# HUM00067750). Successful completion of this proposed study will significantly impact clinical practice and enhance patients’ lives. More broadly, this trial will develop a network of collaboration from which further high-quality trials in ultrasound-guided interventions will follow.

Article Summary

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Magnitude of the Problem

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Lateral Epicondylitis (“Tennis Elbow”) Treatment Options

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The Promise of PRP

Biologic Rationale for Use

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PRP: Emerging Evidence, Lack of Definitive Results

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Need for Definitive Evidence

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Summary: Rationale for a Definitive RCT

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Materials and Methods

Study Design

Overview of Study Design

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Figure 1, IMPROVE study logo.

Table 1

Summary of Study Design for the IMPROVE Study

PRP, platelet-rich plasma; PT, physical therapy.

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The Principal Research Questions

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Eligibility Criteria

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Recruitment and Screening

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Allocation of Patients to Study Groups

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Sonographic Assessment

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Table 2

Diagnostic Ultrasound Features for the IMPROVE Study

Diagnostic Feature Description Measurement Tendon echogenicity The degree of tendinosis is graded based on changes in tendon echotexture Grade 0: normal (excluded)

Grade 1: (mild) ill-defined abnormal hypoechogenicity

Grade 2: (moderate) well-defined abnormal echogenicity

Grade 3: (severe) well-defined abnormal hypoechogenicity and anechoic clefts

Grade 4: (complete) full-width disruption or tear (excluded)

( Fig 3 ) Gray scale abnormality dimensions The greatest dimensions of the gray scale abnormality are measured in millimeters using this axis (1) Short axis

(2) Long axis Tendon thickness The maximal tendon thickness is measured in millimeters at the base of the lateral epicondyle, perpendicular to tendon, with transducer long axis to tendon ( Fig 4 ) Radial collateral ligament (RCL) The gray scale abnormality is described as involving the RCL or not involving the RCL ( Fig 5 ) Tendon hyperemia (involving gray scale abnormality long axis to tendon) The degree of blood flow to the tendon is measured by both color and power Doppler ultrasound None

Mild: a few pixels

Moderate: <50% of the tendon

Severe: >50% of the tendon

( Fig 6 ) Cortical irregularity of common extensor tendon The common extensor tendon footprint is described as having cortical irregularity or not having cortical irregularity Intratendinous calcification The intratendinous calcification is measured in millimeters at the largest dimension and graded None

Hyperechoic with shadowing

Hyperechoic without shadowing Enthesophyte The presence or lack of enthesophyte(s) is recorded

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Figure 2, Postprocedural physical therapy exercise program. All patients undergo the same physical therapy regimen and are given detailed instructions, the above pamphlet, and a Theraband following the procedure.

Figure 3, Various degrees of abnormal tendon echogenicity. (a) Grade 1 (mild): ill-defined abnormal hypoechogenicity; (b) Grade 2 (moderate): well-defined abnormal hypoechogenicity; and (c) Grade 3 (severe): well-defined abnormal hypoechogenicity with anechoic clefts. H, humerus (lateral epicondyle); R, radial head.

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Figure 4, Measurement of tendon thickness. The thickest portion of the tendon is measured from the surface to the base of the lateral epicondyle ( arrowheads ). The line is drawn perpendicular to the tendon fibrils. This measurement encompasses both the common extensor tendon and the radial collateral ligament.

Figure 5, The radial collateral ligament ( arrowheads ) lies deep to the common extensor ( curved arrows ) and occupies ∼50% of the lateral epicondyle footprint ( straight arrows ). a, annular ligament; H, humerus (lateral epicondyle); R, radial head.

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Figure 6, Assessment of tendon hyperemia using color Doppler. (a) Moderate: hyperemia encompassing <50% of the tendon and (b) Severe: hyperemia involving >50% of the tendon thickness. Mild ( not shown ) involves only a few pixels.

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Study Interventions

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Group A: PRP injection (+ physical therapy)

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Group B: whole blood injection (+ physical therapy)

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Group C: dry needle tendon fenestration (+ physical therapy)

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Group D: sham injection and physical therapy alone

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Bilateral Lateral Epicondylitis

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Blinding

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Threshold Performance for Expertise in Performing Autologous Blood Injections

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Periprocedural Treatment

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Outcome Measures

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Patient Follow-up

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Maximization of Follow-up

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Crossovers, Contamination, and Cointerventions

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Sample Size Consideration

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Data Analysis Plan

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Data Safety Monitoring Board

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Potential Impact of Study

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Acknowledgments

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Academic Radiology, Volume 21, Issue 9
Journals General Radiology
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