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

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

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.

Study Overview

• Status: Unknown
• Conditions: Osteoarthritis Of Knee
• Intervention / Treatment: Device: Placebo; Device: Intra-Articular Hyaluronic Acid

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.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Alexandre Sepriano, MD; Email: alexsepriano@gmail.com

Study Locations

• Portugal
  • Lisbon, Portugal
    • Recruiting
    • Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz
    • Contact: Jaime Branco, MD, PhD; Phone Number: 00351 - 21 043 10 00
    • Principal Investigator: Jaime C Branco, MD, PhD
    • Sub-Investigator: Fernando Pimentel-Santos, MD, PhD
    • Sub-Investigator: Alexandre Sepriano, MD
    • Sub-Investigator: João L Gomes, MD
    • Sub-Investigator: Teresa Pedrosa, MD
    • Sub-Investigator: Sofia Serra, MD
    • Sub-Investigator: Sandra Falcão, MD
  • Lisbon, Portugal
    • Recruiting
    • Centro Hospitalar Lisboa Norte
    • Contact: Helena Canhão, MD, PhD; Phone Number: 00351 - 21 780 5000
    • Principal Investigator: Helena Canhão, MD,PhD
    • Sub-Investigator: Maria João Gonçalves, MD
    • Sub-Investigator: Vasco Romão, MD
    • Sub-Investigator: Nikita Khmelinskii, MD
    • Sub-Investigator: Sílvia Silva, MD
    • Sub-Investigator: Joaquim Polido-Pereira, MD
    • Sub-Investigator: Alice Morais Castro, MD
    • Sub-Investigator: Fernando Saraiva, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intra-Articular Hyaluronic Acid; hylan G-F 20 (high molecular weight hyaluronic acid): intra-articular administration; 6 mL; administered every 6 months; for 2 years	Device: Intra-Articular Hyaluronic Acid; Other Names: hylan GF-20
PLACEBO_COMPARATOR: Placebo; Saline solution: intra-articular administration; 6 mL; administered every 6 months; for 2 years	Device: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Joint Space Width	Mean change of minimal JSW of the most affected compartment of the tibiofemural joint in both placebo and IAHA groups at the end of follow-up (2 years).	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OMERACT/OARSI 2004 response	Proportion of patients achieving symptomatic relief according to OMERACT/OARSI 2004 response criteria at 6 months of follow-up in both placebo and IAHA groups. OMERACT/OARSI 2004 will be determined using KOOS questionnaire.	6 months
OMERACT/OARSI 2004 response	Proportion of patients achieving symptomatic relief according to OMERACT/OARSI 2004 criteria at each follow-up visit. OMERACT/OARSI 2004 will be determined using KOOS questionnaire.	2 years
Ocurrence of Knee replacement surgery	Proportion of patients submitted to knee replacement surgery at the end of follow-up	2 years
Acetaminophen Consumption	Mean consumption of acetaminophen (mg/day) at each follow-up visit.	2 years
NSAIDs	Mean consumption of NSAIDs (mg/day) at each follow-up visit.	2 years
SF-36 questionnaire - Physical Score	Mean score of SF-36 questionnaire at each follow-up visit.	2 years
SF-36 questionnaire - Mental Score	Mean score of SF-36 questionnaire at each follow-up visit.	2 years
Euro QoL 5D	Mean score of Euro QoL 5D questionnaire at each follow-up visit.	2 years
Adverse events	Total number of adverse events occurring on both placebo and IAHA groups at each follow-up visit.	2 years
Visual Analog Scale	Mean VAS score at 2 years	2 years
Visual Analog Scale	Mean VAS score at each follow-up visit.	2 years

Collaborators and Investigators

• Sponsor: Universidade Nova de Lisboa
• Collaborators: Hospital de Santa Maria, Portugal; NOVA Medical School; Hospital de Egas Moniz; Instituto de Medicina Molecular João Lobo Antunes; Centro de Estudos de Doenças Crónicas
• Investigators: Principal Investigator: Jaime C Branco, MD, PhD, CEDOC; Study Director: Alexandre Sepriano, MD, Centro Hospitalar de Lisboa Ocidental; Study Chair: João Gomes, MD, Centro Hospitalar de Lisboa Ocidental

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (ANTICIPATED): January 1, 2018
• Study Completion (ANTICIPATED): January 1, 2018

Study Registration Dates

• First Submitted: October 29, 2014
• First Submitted That Met QC Criteria: October 30, 2014
• First Posted (ESTIMATE): October 31, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): November 2, 2014
• Last Update Submitted That Met QC Criteria: October 31, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Knee Osteoarthritis; Intra-Articular Hyaluronic Acid; disease modifying
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid
• Other Study ID Numbers: NOVA-FCM-Rheuma-2