Combining two Hyaluronic Acids with different characteristics: a randomised, double-blind, placebo controlled trial

ISRCTN	ISRCTN98630331
DOI	https://doi.org/10.1186/ISRCTN98630331
Protocol serial number	N/A
Sponsor	Lawson Health Research Institute (Canada)
Funder	Lawson Health Research Institute (Canada)

Submission date: 23/10/2007
Registration date: 30/10/2007
Last edited: 28/10/2008

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Robert Petrella
Scientific

801 Commissioners Road
Suite 3002
London
N6C 5J1
Canada

Study information

Primary study design	Interventional
Study design	Randomised, placebo-controlled, double-blind prospective design
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	2 HAs
Study objectives	Combined Hyaluronic Acids (HA) will improve clinical outcomes more than a single HA.
Ethics approval(s)	Ethics approval received from the Research Ethics Board of the University of Western Ontario on the 10th September 2006 (ref: # 166732).
Health condition(s) or problem(s) studied	Osteoarthritis of the knee
Intervention	Patients were randomised to receive one of four treatments: 1. Lower Molecular Weight HA (LMW) 2. Higher Molecular Weight HA (HMW) 3. Combined lower and higher molecular weight and different concentrations (DMW) 4. Saline placebo Physicians and patients were blinded to assignment (syringes were covered to conceal any details of product or volume). Low molecular weight solution of HA was a marketed product of 0.50 - 0.73 x 10^6 Daltons and the high molecular weight HA was a marketed product of 6 million kDa, both indicated for intra-articular injection for knee osteoarthritis. 2 ml of LMW and HMW were injected using an aseptic technique and a medial approach. No anaesthetic was used either topically or intra-articularly. Each injection was performed one week apart (± 2 days) by an experienced clinician. All injections were initiated after baseline and follow-up assessments of Visual Analogue Scale (VAS) and global satisfaction which were performed by an independent technician. The DMW preparation consisted of 0.7 ml of sterile 2.2% LMW (0.58 - 0.78 x 10^6 Daltons) sodium hyaluronate and 0.7 ml of sterile 1% HMW (1.2 - 2.0 x 10^6 Daltons) sodium hyaluronate. Viscoelastics were separated by a Debiopass stopper within a pre-filled 3 ml sterile syringe. Injection was conducted as for the LMW and HMW preparations as described above. Patients were free to seek additional therapeutic modalities including physical therapy and analgesics (including Non-Steroidal Anti-Inflammatory Drugs [NSAIDs]) but not intra-articular therapies prior to their presentation for follow-up. All concomitant treatments were recorded. All assessments were conducted at baseline V1, and prior to each injection at visits 2, 3 and 4, and follow-up visits at 4 (V5), 12 (V6) and 16 (V7) weeks.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Hyaluronic Acid
Primary outcome measure(s)	Improvement in self-paced 40-m walking pain using the Visual Analogue Scale (VAS), measured at V1 - V7. Timepoints: V1 = Baseline V2 = Week 1 V3 = Week 2 V4 = Week 3 V5 = Week 4 V6 = Week 12 V7 = Week 16
Key secondary outcome measure(s)	1. Improvement in seated rest pain Visual Analogue Scale (VAS), measured at V1 - V7 2. Patient global satisfaction using a 5-point numerical scale, with 1 representing not satisfied and 5 completely satisfied, measured at V1 - V7 3. Presence of adverse events and concomitant medications, measured at V1 - V7 Timepoints: V1 = Baseline V2 = Week 1 V3 = Week 2 V4 = Week 3 V5 = Week 4 V6 = Week 12 V7 = Week 16
Completion date	01/07/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	200
Key inclusion criteria	1. Radiographic evidence of grade 1 to 3 medial compartment Osteoarthritis (OA) 2. Did not exhibit non-arthritis related disease 3. Gave consent as approved by the University of Western Ontario Ethics Review Board 4. Age range at recruitment was 45 - 85 years, both men and women
Key exclusion criteria	1. Previous injection with HA or corticosteroids 2. Bilateral knee OA 3. Unstable cardiovascular or metabolic disease 4. Unable to commit to follow-up period
Date of first enrolment	01/01/2007
Date of final enrolment	01/07/2007

Locations

Countries of recruitment

Canada

Study participating centre

801 Commissioners Road

London
N6C 5J1
Canada

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/08/2008		Yes	No