Platelet Rich Plasma Injection for Knee Osteoarthritis

Platelet Rich Plasma In Knee Osteoarthritis: A Prospective, Double-Blind Randomized, Placebo Controlled Clinical Trial

The research questions of this study are;

1. Is platelet rich plasma (PRP) treatment effective in knee osteoarthritis (OA)?
2. What are the indications for PRP treatment?
3. Which patients are the most suitable for the PRP treatment method?
4. How does age, Body Mass Index (BMI), lower extremity mechanical axis angle and OA stages affect the success of the PRP treatment?
5. Is there any advantage of multiple PRP doses?
6. What is the therapeutic effect of placebo?

This study was designed to find answers of these questions.

The hypotheses of this study are; "PRP treatment is more effective than placebo; PRP treatment effectiveness decreases with age and advanced stages of OA; BMI is a factor that negatively affects the treatment effectiveness of the PRP; as the mechanical axis angle of the lower limb increases, it will adversely affect the effectiveness of PRP therapy; multiple dose of PRP affects the effectiveness and duration of PRP as positively compared to single dose of PRP".

The primary purpose of this study; to prove the effectiveness of PRP treatment on knee pain and functions in patients with knee OA by comparing it with the placebo control group. Secondary purposes of this study; to understand the effect of age, BMI, OA grade and lower limb mechanical axis angle on PRP effectiveness. This study, designed as a randomized, double-blind and placebo control group, with a high level of scientific evidence. Thus, it will be scientifically possible to find answers to the investigators research questions and to prove the investigators hypothesis.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis; Cartilage Degeneration
• Intervention / Treatment: Biological: PRP; Drug: Saline

Detailed Description

The power analysis of this study was calculated based on the sample size studies of previous studies. The difference of d = 3 units between the two means is to have a standard deviation of 6 units. The sample size 200 required to detect with 95% power in the 95% confidence interval to detect.

This study covers 324 patients. All patients were selected according to predefined and established inclusion and exclusion criteria.

Inclusion criteria were: stage 1-2-3 symptomatic OA patients according to Kellgren / Lawrence staging, age between 18 and 80 years, mean Visual Analogue Score (VAS) of >4 of 10 (worst possible pain) over the course of 7 days during the previous month were included on a voluntary basis. Only one knee injection was made to the patients.

Exclusion criteria were OA secondary to joint inflammatory diseases; patients with generalized OA, metabolic diseases of the bone, coexisting backache, the presence of hematological disease (coagulopathy), bilateral symptomatic lesions and advanced stages (grade 4) of OA; patients who had received intra-articular injections within three months or arthroscopic lavage in the previous one year or who were receiving immunosuppressive; patients with current use of anticoagulant medications or NSAIDs used in the five days before blood donation, major axis deviation (more than 15 degree of varus or more than 5 degree of valgus deviation); and patients with a hemoglobin level less than 11.5 g/dL and platelets level less than 100,000/μL or associated co-morbidities, infection, tumor, crystal arthropathies, anemia, tense joint effusion and pregnancy or possibility of pregnancy.

The voluntary patients included in this study were divided into four different groups with a computer-assisted randomization program. This groups; group A (n:67) were given a single injection of PRP, group B (n:69) were given a single injection of normal saline (physiological control/placebo), group C (n:66) were given three injection (one per month) of PRP, group D (n:65) were given three injection of normal saline (one per month) (physiological control/placebo).

All patients were evaluated by a blinded researcher with VAS, Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), KUJALA, knee range of motion (ROM) and knee circumference measurement at 1st, 3rd, 6th, 12th and 24th months after treatment.

• Study Type: Interventional
• Enrollment (Actual): 324
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Turkey
  • Atakum
    • Samsun, Atakum, Turkey, 55139
      • Department of Orthopedic and Trauma, Faculty of Medicine, Ondokuz Mayıs University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• stage 1-2-3 symptomatic OA patients according to Kellgren / Lawrence staging
• mean VAS pain score of >4 of 10 (worst possible pain) over the course of 7 days during the previous month

Exclusion Criteria:

• OA secondary to joint inflammatory diseases,
• generalized OA,
• metabolic diseases of the bone,
• coexisting backache,
• the presence of hematological disease (coagulopathy),
• bilateral symptomatic lesions and advanced stages (grade 4) of OA,
• patients who had received intra-articular injections within 3 months or arthroscopic lavage in the previous 1 year,
• patients who were receiving immunosuppressive,
• patients with current use of anticoagulant medications,
• NSAIDs used in the 5 days before blood donation,
• major axis deviation (more than 15 degree of varus or more than 5 degree of valgus deviation),
• patients with a hemoglobin level less than 11.5 g/dL,
• platelets level less than 100,000/μL,
• associated comorbidities, infection, tumor, crystal arthropathies, anemia, tense joint effusion and pregnancy or possibility of pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRP group; Intraarticular 5 ml single PRP injection	Biological: PRP; platelet rich plasma; Other Names: platelet rich plasma
Placebo Comparator: Saline group; Intraarticular 5 ml single saline injection	Drug: Saline; serum physiologic; Other Names: serum physiologic
Experimental: Multiple PRP group; Intraarticular 3 dose of 5 ml PRP injection (0, 1, 3 month injection)	Biological: PRP; platelet rich plasma; Other Names: platelet rich plasma
Placebo Comparator: Multiple saline group; Intraarticular 3 dose of 5 ml saline injection (0, 1, 3 month injection)	Drug: Saline; serum physiologic; Other Names: serum physiologic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS	Visual Analogue scale (0-10 higher scores mean a worse outcome)	Baseline VAS score
VAS	Visual Analogue scale (0-10 higher scores mean a worse outcome)	VAS score at 1st months
VAS	Visual Analogue scale (0-10 higher scores mean a worse outcome)	VAS score at 3th months
VAS	Visual Analogue scale (0-10 higher scores mean a worse outcome)	VAS score at 6th months
VAS	Visual Analogue scale (0-10 higher scores mean a worse outcome)	VAS score at 12th months
VAS	Visual Analogue scale (0-10 higher scores mean a worse outcome)	VAS score at 24th months
KOOS	Knee injury and Osteoarthritis Outcome Score (0-100 higher scores mean a better outcome)	Baseline KOOS score
KOOS	Knee injury and Osteoarthritis Outcome Score (0-100 higher scores mean a better outcome)	KOOS score at 1st months
KOOS	Knee injury and Osteoarthritis Outcome Score (0-100 higher scores mean a better outcome)	KOOS score at 3th months
KOOS	Knee injury and Osteoarthritis Outcome Score (0-100 higher scores mean a better outcome)	KOOS score at 6th months
KOOS	Knee injury and Osteoarthritis Outcome Score (0-100 higher scores mean a better outcome)	KOOS score at 12th months
KOOS	Knee injury and Osteoarthritis Outcome Score (0-100 higher scores mean a better outcome)	KOOS score at 24th months
WOMAC	Western Ontario and McMaster Universities Arthritis Index (0-100 higher scores mean a better outcome)	Baseline WOMAC score
WOMAC	Western Ontario and McMaster Universities Arthritis Index (0-100 higher scores mean a better outcome)	WOMAC score at 1st months
WOMAC	Western Ontario and McMaster Universities Arthritis Index (0-100 higher scores mean a better outcome)	WOMAC score at 3th months
WOMAC	Western Ontario and McMaster Universities Arthritis Index (0-100 higher scores mean a better outcome)	WOMAC score at 6th months
WOMAC	Western Ontario and McMaster Universities Arthritis Index (0-100 higher scores mean a better outcome)	WOMAC score at 12th months
WOMAC	Western Ontario and McMaster Universities Arthritis Index (0-100 higher scores mean a better outcome)	WOMAC score at 24th months
Kujala	Kujala Patellofemoral Score (0-100 higher scores mean a better outcome)	Baseline Kujala score
Kujala	Kujala Patellofemoral Score (0-100 higher scores mean a better outcome)	Kujala score at 1st months
Kujala	Kujala Patellofemoral Score (0-100 higher scores mean a better outcome)	Kujala score at 3th months
Kujala	Kujala Patellofemoral Score (0-100 higher scores mean a better outcome)	Kujala score at 6th months
Kujala	Kujala Patellofemoral Score (0-100 higher scores mean a better outcome)	Kujala score at 12th months
Kujala	Kujala Patellofemoral Score (0-100 higher scores mean a better outcome)	Kujala score at 24th months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee movement	knee joint range of motion (measured by goniometer as degree)	1st, 3rd, 6th, 12th and 24th months
knee circumference	Knee Trans patella circumference	1st, 3rd, 6th, 12th and 24th months
mechanical axis angle	angle measured from radiological axes graphs	baseline
age	age of the patient	baseline
stage	stage of the osteoarthritis	baseline
BMI	body mass index	baseline
patient global satisfaction	subjective satisfaction level of the patient	24 months

Collaborators and Investigators

• Sponsor: Ferhat Say

Publications and helpful links

General Publications

• Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013 Feb;41(2):356-64. doi: 10.1177/0363546512471299. Epub 2013 Jan 8.
• Smith PA. Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis: An FDA-Sanctioned, Randomized, Double-blind, Placebo-controlled Clinical Trial. Am J Sports Med. 2016 Apr;44(4):884-91. doi: 10.1177/0363546515624678. Epub 2016 Feb 1.
• Lin KY, Yang CC, Hsu CJ, Yeh ML, Renn JH. Intra-articular Injection of Platelet-Rich Plasma Is Superior to Hyaluronic Acid or Saline Solution in the Treatment of Mild to Moderate Knee Osteoarthritis: A Randomized, Double-Blind, Triple-Parallel, Placebo-Controlled Clinical Trial. Arthroscopy. 2019 Jan;35(1):106-117. doi: 10.1016/j.arthro.2018.06.035.
• Gormeli G, Gormeli CA, Ataoglu B, Colak C, Aslanturk O, Ertem K. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc. 2017 Mar;25(3):958-965. doi: 10.1007/s00167-015-3705-6. Epub 2015 Aug 2.
• Di Martino A, Di Matteo B, Papio T, Tentoni F, Selleri F, Cenacchi A, Kon E, Filardo G. Platelet-Rich Plasma Versus Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis: Results at 5 Years of a Double-Blind, Randomized Controlled Trial. Am J Sports Med. 2019 Feb;47(2):347-354. doi: 10.1177/0363546518814532. Epub 2018 Dec 13.
• Filardo G, Di Matteo B, Di Martino A, Merli ML, Cenacchi A, Fornasari P, Marcacci M, Kon E. Platelet-Rich Plasma Intra-articular Knee Injections Show No Superiority Versus Viscosupplementation: A Randomized Controlled Trial. Am J Sports Med. 2015 Jul;43(7):1575-82. doi: 10.1177/0363546515582027. Epub 2015 May 7.
• Yurtbay A, Say F, Cinka H, Ersoy A. Multiple platelet-rich plasma injections are superior to single PRP injections or saline in osteoarthritis of the knee: the 2-year results of a randomized, double-blind, placebo-controlled clinical trial. Arch Orthop Trauma Surg. 2022 Oct;142(10):2755-2768. doi: 10.1007/s00402-021-04230-2. Epub 2021 Oct 27.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): August 23, 2019
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: June 24, 2020
• First Submitted That Met QC Criteria: June 30, 2020
• First Posted (Actual): July 1, 2020

Study Record Updates

• Last Update Posted (Actual): July 1, 2020
• Last Update Submitted That Met QC Criteria: June 30, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: osteoarthritis; placebo; platelet-rich plasma; growth factors
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: PRP2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No