The present study is designed to test the hypothesis that Intra-Articular Hyaluronic Acid (IAHA) is superior to placebo in slowing structural progression and on long term symptomatic effect in primary knee Osteoarthritis (OA) patients. The investigators will perform a multicenter double-blind, randomized, placebo-controlled, parallel group trial.

Brief Title

Trial to Assess the Structural Effect and Long-term Symptomatic Relief of Intra-articular Injections of Hyaluronic Acid in Primary Knee OA

Official Title

A Randomized Placebo Controlled Trial to Assess the Structural Effect and Long-term Symptomatic Relief of Repeated Intra-articular Injections of Hyaluronic Acid in Primary Knee Osteoarthritis

Brief Summary

The present study is designed to test the hypothesis that Intra-Articular Hyaluronic Acid<br /> (IAHA) is superior to placebo in slowing structural progression and on long term symptomatic<br /> effect in primary knee Osteoarthritis (OA) patients.<br /><br /> The investigators will perform a multicenter double-blind, randomized, placebo-controlled,<br /> parallel group trial.

Detailed Description

The target population will be patients with the diagnosis of knee osteoarthritis who are
followed at two Portuguese hospitals (Centro Hospitalar de Lisboa Norte - Hospital Santa
Maria, Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz).

All patients selected will be included in the intention-to-treat group. Then, using blocked
randomization method they will be assigned to receive either IAHA, or placebo (saline
solution). At both hospitals the study will consist of four injections of IAHA, 6 months
apart, plus a 6 month period after the injection, resulting in a total follow-up period of 24
months. Before each new cycle a follow-up consultation will be performed in order to assess
pain and function (KOOS), quality of life (SF-36), adverse events and consumption of
acetaminophen and NSAIDS regarding the week before evaluation. X-rays will be performed in
the beginning of follow-up, one year after that and 6 months after the last cycle of IAHA or
placebo injections (24 months).

Ultrasound evaluation will be performed at the target knee in same time points as X-rays by
two rheumatologists trained in musculoskeletal ultrasound examination. Additionally, the
investigators will assess potential biochemical biomarkers of knee OA structural progression
and response to treatment. Measurements will be performed in both serum and urine and, If
possible, synovial fluid aspiration will be performed and together with blood and urine
samples stored at the Biobanco-IMM Instituto de Medicina Molecular for analysis. Biologic
samples collection will be performed at baseline and repeated at the 4th, 12th, 24th, 36th
weeks, and then every 6 months.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

Inclusion Criteria:

  -  Symptomatic knee OA as defined by the ACR clinical and radiographic criteria

  -  Kellgren-Lawrence grade of II or III on prior x-rays (taken within 6 months of the
     screen visit) or screen X-ray

  -  A minimum medial and/or lateral JSW of the target knee of 2 mm

  -  Knee pain of 40 mm or greater on a 100 mm visual analogue scale (VAS) at any time
     during the week before inclusion

  -  Oral corticosteroids (≤10 mg/day prednisolone or equivalent), NSAIDs, and
     acetaminophen are permitted if the dose had been stable for at least one month prior
     to baseline

Exclusion Criteria:

  -  Body mass index greater than 40 kg/m2

  -  Varus or valgus deformity of the knee > 15 degrees (assessed by goniometry)

  -  History of trauma, surgery or planned surgery to the study joint (including
     arthroscopy surgery), joint inflammatory diseases, septic arthritis and/or
     microcrystalline arthropathies

  -  Coagulation/platelet disorders

  -  Active malignancy, active systemic infection, or any contraindication to MRI

  -  Potent analgesics including opiates, oral corticosteroid therapy within one month
     prior to enrolment into the study other than stable doses of ≤ 10 mg daily
     prednisolone or equivalent

  -  Knee administration of intra-articular steroids in the previous 3 months or HA
     injections during the past year