Effect of Different Injection Regimens of Autologous Conditioned Plasma for Knee Osteoarthritis

• ClinicalTrials.gov Identifier: NCT03889925
• Recruitment Status: Enrolling by invitation
• First Posted: March 26, 2019
• Last Update Posted: March 10, 2020
• Sponsor: Andrews Research & Education Foundation
• Information provided by (Responsible Party): Andrews Research & Education Foundation

Study Description

Brief Summary:

The clinical efficacy of hyaluronic acid or corticosteroid injections has been reported, but effects are short lived. This has led to the development of additional injection options such as autologous derived blood products which have been documented to alleviate symptoms related to knee osteoarthritis, with recent comparative studies suggesting a greater, long-lasting effect with these blood derived products like platelet rich plasma (PRP) [2-8]. One clinically-developed preparation of platelet rich plasma, named autologous conditioned plasma (ACP), has randomized controlled trial data proving efficacy [4,9]. Clinical use of platelet rich plasma for knee arthritis typically involves a 3-injection series over 3 weeks, i.e. an injection once a week for three weeks. The main objective of this study is to determine if hyaluronic acid (HA) injected at the same time as autologous conditioned plasma (ACP), a leukocyte-poor platelet rich plasma product, will improve the performance of ACP in the treatment of symptomatic knee osteoarthritis. It is hypothesized that the injection of hyaluronic acid will improve the efficacy of ACP.

Condition or disease	Intervention/treatment	Phase
Knee Osteoarthritis	Drug: Hymovis; Biological: Autologous conditioned plasma	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Masking Description: Participants will be blinded to the type of injection that they receive.
• Primary Purpose: Treatment
• Official Title: Effect of Different Injection Regimens of Autologous Conditioned Plasma for the Treatment of Symptomatic Knee Osteoarthritis
• Actual Study Start Date: March 15, 2019
• Estimated Primary Completion Date: March 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Autologous conditioned plasma group; Participants in this group will receive a three-injection series of autologous conditioned plasma over the course of 3 consecutive weeks.	Biological: Autologous conditioned plasma; Patients will receive 3 intra-articular injections of autologous conditioned plasma dosed at once a week for 3 weeks.
Experimental: Autologous conditioned plasma with hyaluronic acid group; Participants in this group will receive a two-injection series of autologous conditioned plasma and hyaluronic acid (Hymovis, Fidia Pharmaceuticals) and a third injection on the third week of autologous conditioned plasma.	Drug: Hymovis; Patients will receive 2 intra-articular injections of autologous conditioned plasma and hyaluronic acid once a week for 2 weeks and a third injection on the third week of ACP.

Outcome Measures

Primary Outcome Measures :

1. Change in Western Ontario and McMaster University's Osteoarthritis Index (WOMAC) [ Time Frame: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post injections ]
   Patient reported outcome measure; The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total score. Higher scores indicate worse pain, stiffness, and functional limitations.
2. Change in International Knee Documentation Committee Subjective Knee Evaluation Form [ Time Frame: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post injections ]
   Patient reported outcome measure; Scores are obtained by summing the individual items, then transforming the crude total to a scaled number that ranges from 0 to 100. This final number is interpreted as a measure of function with higher scores representing higher levels of function.
3. Change in Knee Injury and Osteoarthritis Outcome Score [ Time Frame: Baseline, 1 month, 3 months, 6 months, 12 months, 18 months, and 24 months post injections ]
   Patient reported outcome measure; Consists of 5 subscales; Pain, other Symptoms, Function in daily living, Function in sport and recreation and knee related Quality of life. each question is assigned a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale.

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients between the ages of 30 and 80
• Documented radiographic evidence of OA in the tibiofemoral or patellofemoral compartment of the involved knee (Kellgren-Lawrence grades 1-4)
• Patients must have a documented diagnosis of primary OA for at least 6 weeks.

Exclusion Criteria:

• Patients who have had viscosupplementation in the involved knee in the past 6 months.
• Any patient who has had a corticosteroid injection in any joint within 3-months prior to screening will be excluded.
• Patients with gout or rheumatologic disease will be excluded. Patients who have had a previous negative experience with HA.
• Any patient who will have difficulty obtaining internet access, does not have an active e-mail address, or is unable to comprehend study documents or give informed consent will be excluded.

Contacts and Locations

Locations

United States, Florida

Andrews Institute for Orthopaedics & Sports Medicine

Gulf Breeze, Florida, United States, 32561

Sponsors and Collaborators

Andrews Research & Education Foundation

  Study Documents (Full-Text)

Documents provided by Andrews Research & Education Foundation:

Study Protocol and Statistical Analysis Plan  [PDF] June 19, 2019

Informed Consent Form  [PDF] June 27, 2019

More Information

Publications:

Spakova T. Re: Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid. Am J Phys Med Rehabil. 2014 Jan;93(1):95.

Kon E, Mandelbaum B, Buda R, Filardo G, Delcogliano M, Timoncini A, Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: from early degeneration to osteoarthritis. Arthroscopy. 2011 Nov;27(11):1490-501. doi: 10.1016/j.arthro.2011.05.011. Epub 2011 Aug 10.

Cerza F, Carnì S, Carcangiu A, Di Vavo I, Schiavilla V, Pecora A, De Biasi G, Ciuffreda M. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med. 2012 Dec;40(12):2822-7. doi: 10.1177/0363546512461902. Epub 2012 Oct 25.

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.

Li M, Zhang C, Ai Z, Yuan T, Feng Y, Jia W. [Therapeutic effectiveness of intra-knee-articular injection of platelet-rich plasma on knee articular cartilage degeneration]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 Oct;25(10):1192-6. Chinese.

Filardo G, Kon E, Di Martino A, Di Matteo B, Merli ML, Cenacchi A, Fornasari PM, Marcacci M. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord. 2012 Nov 23;13:229. doi: 10.1186/1471-2474-13-229.

Vaquerizo V, Plasencia MÁ, Arribas I, Seijas R, Padilla S, Orive G, Anitua E. Comparison of intra-articular injections of plasma rich in growth factors (PRGF-Endoret) versus Durolane hyaluronic acid in the treatment of patients with symptomatic osteoarthritis: a randomized controlled trial. Arthroscopy. 2013 Oct;29(10):1635-43. doi: 10.1016/j.arthro.2013.07.264.

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.

• Responsible Party: Andrews Research & Education Foundation
• ClinicalTrials.gov Identifier: NCT03889925
• Other Study ID Numbers: 1379083
• First Posted: March 26, 2019
• Last Update Posted: March 10, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases