Leukocyte-rich PRP or Leukocyte-free PRP vs Placebo in the Treatment of Epicondylitis

Official title

Leukocyte-rich PRP or Leukocyte-free PRP vs Placebo in the Treatment of Epicondylitis: a Randomized Controlled Clinical Trial

Overview

The EPIC-PRP study is a double-blind randomized controlled clinical trial with 1:1:1 allocation.The objective of the study is to evaluate by means of a randomized controlled, double-blind clinical trial the clinical outcomes of echo-guided injection of PRP with or without leukocytes compared with echo-guided injection of saline for minimally invasive treatment of patients with epicondylitis resistant to conservative therapy. It will be the aim of the study to evaluate the efficacy and safety of the injection procedures by revealing the improvement and incidence of adverse events following treatment

Detailed description

Patients with elbow epicondylitis will be included in a double-blind, randomized controlled trial, in which one group of patients will be treated with an echo-guided injection of LP-PRP (low leukocyte PRP), one group of patients will be treated with an echo-guided injection of LR-PRP (high leukocyte PRP), and another group of patients will be treated with an echo-guided injection of saline.All enrolled patients undergo sampling of a venous whole blood bag of approximately 300 cc from which Fresh Autologous PRP (PRP-A) will subsequently be obtained. According to randomization, a "leukodepletion" filter will be used to remove leukocytes in order to obtain LP-PRP. Instead, an aliquot of PRP will be cryopreserved and made available for the patient for a possible second PRP infiltration if there is no benefit after 6 months after the first infiltration.The patient will then be placed on the randomization list and will, therefore, be assigned to one of the three treatment groups (leukocyte-rich PRP, leukocyte-poor PRP, or saline solution). In the case of patients in the saline injection group, PRP will be prepared with or without leukocytes according to a dedicated randomization list, for possible treatment after 6 months if necessary.The patient will subsequently undergo 1 echo-guided infiltration, according to randomization.Patients will be clinically evaluated before the infiltration procedure and at 1-3-6-12 months after treatment by medical personnel. Questionnaires will be administered for clinical evaluations before treatment and at the above-mentioned clinical checkups during follow-up. Any adverse events to treatment will also be evaluated during follow-up visits. The duration and extent of swelling and pain following infiltration will be reported, and any drug therapies given by the patient will be recorded

Interventions

• Biological Injection of autologous leukocyte rich platelet rich plasma (LR-PRP)
  Patients will be treated with a single eco-guided injection of Autologous LR-PRP in the elbow affected by epicondylitis.
• Biological Injection of autologous leukocyte poor platelet rich plasma (LP-PRP)
  Patients will be treated with a single eco-guided injection of Autologous LP-PRP in the elbow affected by epicondylitis.
• Drug Placebo (saline solution)
  Patients will be treated with a single injections of saline solution in the elbow affected by epicondylitis.

Primary outcome measures

• Patient-rated Tennis Elbow Evaluation (PRTEE) [Time frame: 6 months follow-up]

Secondary outcome measures (12)

• Patient-rated Tennis Elbow Evaluation (PRTEE) [Time frame: baseline, 1 month, 3 months and 12 months follow-up]
• Disability of the arm, shoulder and hand score (DASH) [Time frame: baseline, 1 month, 3 months, 6 months and 12 months follow-up]
• Tegner Activity Level Scale [Time frame: baseline, 1 month, 3 months, 6 and 12 months follow-up]
• Oxford Elbow Score (OES) [Time frame: baseline, 1 month, 3 months, 6 and 12 months follow-up]
• Visual Analogue Scale (VAS) [Time frame: baseline, 1 month, 3 months, 6 and 12 months follow-up]
• EuroQol Visual Analogue Scale (EQ-VAS) [Time frame: baseline, 1 month, 3 months, 6 and 12 months follow-up]
• EQ-5D (EuroQoL) Current Health Assessment [Time frame: baseline, 1 month, 3 months, 6 and 12 months follow-up]
• Pain detect [Time frame: baseline]
• Patient Acceptable Symptom State (PASS) [Time frame: baseline, 1 month, 3 months, 6 and 12 months follow-up]
• Final treatment opinion [Time frame: 1 month, 3 months, 6 and 12 months follow-up]
• Effectiveness of the blinding procedure [Time frame: baseline]
• Expectations of treatment efficacy [Time frame: baseline]

Eligibility criteria

Inclusion criteria

Patients with epicondylitis of the elbow:

• Patients with clinical picture of epicondylitis;
• Duration of symptoms > 3 months
• Ultrasound picture of short or long radial extensor carpal tendinopathy;
• Age > 18 and < 65
• Both sexes;
• Failure, defined as persistence of symptoms, of other conservative treatments for at least 3 months;
• Hemoglobin > 11 g/dl;
• Platelet count > 150,000 plt/mm3 (Recently performed CBC examination);
• Negative serological tests for HBsAg, HCV Ab, HIV-1-2 Ab
• No clinically significant electrocardiographic changes (Recently performed ECG);
• Ability and consent of the patient to actively participate in clinical follow-up;
• Signature of informed consent.

Exclusion criteria

• Patients undergoing previous surgical treatment on the epicondylar tendons;
• Patients undergoing epicondylar infiltration in the previous 6 months;
• Inability of patients to actively participate in clinical follow-up;
• Incapacitated patients;
• Patients with states of immunodepression;
• Patients with fibromyalgia;
• Ongoing systemic inflammatory diseases (stabilized outcomes of such diseases are not considered absolute contraindications);
• Patients with uncontrolled thyroid metabolic disorders;
• Patients abusing alcoholic beverages, drugs or medications;
• Patients who have taken NSAIDs in the 3 days prior to blood collection;
• Patients with coagulation problems or with ongoing antiplatelet therapy that cannot be suspended for at least 3 days prior to blood draw;
• Patients with cardiovascular disease for whom a 300-mL blood draw would be contraindicated;
• Positive serological tests for HBsAg, HCV Ab, HIV-1-2 Ab
• Other current elbow diseases (osteoarthritis, prevalence of symptomatology due to epitrochleitis, stiff elbow, etc.)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• Istituto Ortopedico Rizzoli — Bologna

Publications

• Kim GM, Yoo SJ, Choi S, Park YG. Current Trends for Treating Lateral Epicondylitis. Clin Shoulder Elb. 2019 Dec 1;22(4):227-234. doi: 10.5397/cise.2019.22.4.227. eCollection 2019 Dec. PMID 33330224
• Chen J, Wang A, Xu J, Zheng M. In chronic lateral epicondylitis, apoptosis and autophagic cell death occur in the extensor carpi radialis brevis tendon. J Shoulder Elbow Surg. 2010 Apr;19(3):355-62. doi: 10.1016/j.jse.2009.07.064. PMID 19836974
• Hsu WK, Mishra A, Rodeo SR, Fu F, Terry MA, Randelli P, Canale ST, Kelly FB. Platelet-rich plasma in orthopaedic applications: evidence-based recommendations for treatment. J Am Acad Orthop Surg. 2013 Dec;21(12):739-48. doi: 10.5435/JAAOS-21-12-739. PMID 24292930
• Chen X, Jones IA, Park C, Vangsness CT Jr. The Efficacy of Platelet-Rich Plasma on Tendon and Ligament Healing: A Systematic Review and Meta-analysis With Bias Assessment. Am J Sports Med. 2018 Jul;46(8):2020-2032. doi: 10.1177/0363546517743746. Epub 2017 Dec 21. PMID 29268037
• Karaduman M, Okkaoglu MC, Sesen H, Taskesen A, Ozdemir M, Altay M. Platelet-rich plasma versus open surgical release in chronic tennis elbow: A retrospective comparative study. J Orthop. 2016 Jan 22;13(1):10-4. doi: 10.1016/j.jor.2015.12.005. eCollection 2016 Mar. PMID 26955228

Identifiers

NCT: NCT06040203 · Epic-PRP

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗