Platelet Rich plasma Injection Management for Ankle osteoarthritis study (PRIMA): A multi-center, stratified, block-randomized, double-blind, placebo-controlled trial

Pain is the cardinal symptom of ankle osteoarthritis (OA) and is a complex
phenomenon with limited understanding of its pathomechanisms. The main
objectives in the clinical management of OA are to reduce inflammation and
cartilage degeneration processes and relieve pain.
A recent review concluded that in animal models platelet rich plasma (PRP) can
diminish multiple inflammatory IL-1 mediated effects, and can also positively
influence the collagen network of the cartilage and subsequently reduce pain
and improve function.
Our recent and other systematic reviews showed that compared to placebo
injections, hyaluronic acid or corticosteroid injections, PRP injections
significantly decrease pain and improve function in knee OA. Given the clinical
effect on pain reduction in OA and safety, PRP might serve as a promising
non-surgical therapy and might potentially delay the irreversible surgical
option of arthrodesis.

The goal of this study is to determine the efficacy of PRP injections in the
management of ankle osteoarthritis by comparing 2 groups: One receiving a PRP
injection and the other a saline solution.

A multi*center, stratified, block*randomized, double*blind, placebo*controlled
trial comparing two treatment groups.

In this study, patients will be randomised into two treatment groups: PRP
injection or placebo injection. Treatment allocation will be concealed. Two
double syringes of autologous blood will be collected twice with from the
cubital vein: at inclusion and at a time interval of 6 weeks. This blood will
be prepared according to the instructions of the manufacturer (see below PRP
preparation), and the injection will be given within 30 minutes after
preparation. For each injection 2 ml will be injected into the affected ankle
joint under ultrasonographic guidance. The control group will follow exactly
the same protocol of vena puncture and preparation of the PRP, but instead of
PRP, 2ml physiological saline will be injected on each occasion. To guarantee
blinding for the allocated treatment of the patient, treatment assessor and
treating physician, blood will be drawn and PRP will be prepared for each
patient during both injections (at inclusion and at a time interval of 6 weeks
after the first injection). A research assistant will select one of the two
syringes based on the allocated intervention and blinds the syringe with a
covering sheath.

Complications have not been observed in previous studies with the same
intervention performed on different locations. The PRP injection may be painful
but similar to other inta-articular injections. Although no adverse effects
have been previously reported, no guarantee can be given for intra-articular
ankle injections. On inclusion, participants will undergo ankle x-rays. The
expected radiation and risks to the participant as a result are negligible.