A Study of Hyaluronan for the Treatment of Osteoarthritis in the Thumb

• Sponsor: Hospital for Special Surgery, New York (Other)
• Overall Status: Completed
• CT.gov ID: NCT00398866
• Collaborator: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH), Genzyme, a Sanofi Company (Industry)
• Enrollment: 200
• Location: 1
• Arms: 3
• Duration (Months): 79
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

Hyaluronan is a man-made preparation of a protein complex that occurs naturally in joints and that is often low in people with osteoarthritis. Although hyaluronan has been used in millions of people with knee osteoarthritis, it is not yet FDA approved for use in the thumb. The purpose of this study is to determine the safety and effectiveness of hyaluronan in relieving arthritis symptoms at the base of the thumb and to compare it to corticosteroids and local anesthetic.

The principle hypothesis is that treating osteoarthritis at the carpometacarpophalangeal (CMC) joint with injectable hyaluronan will results in greater pain relief, higher patient satisfaction, and better functional outcomes than treating with placebo injections (local anesthetic) or with corticosteroid injections. Treating CMC osteoarthritis with corticosteroid injections will result in greater pain relief, higher patient satisfaction, and better functional outcomes than treating with placebo injections. Patients with worse pre-treatment function will have less improvement and worse post-treatment results after administration of corticosteroid or hyaluronan.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis	Drug: Synvisc (Hylan G-F20; hyaluronan injection); Drug: Bupivicaine (local anesthesia injection); Drug: Kenalog (triamcinolone; corticosteroid injection)	Phase 3

Detailed Description

Osteoarthritis involves a wearing down of the cartilage within a joint. It can affect any joint in the body, but it most commonly affects joints in the hands, hips, knees, and spine. Over the last few years, a new medicine called hyaluronan has been used for treating osteoarthritis. Hyaluronan is a man-made preparation of a protein complex that occurs naturally in joints and that is often low in people with osteoarthritis. Although hyaluronan has been used in millions of people with knee osteoarthritis, it is not yet FDA approved for use in the thumb. The purpose of this study is to determine the safety and effectiveness of hyaluronan in relieving arthritis symptoms at the base of the thumb and to compare it to corticosteroids and local anesthetic. Specifically, the study will evaluate pain relief, patient satisfaction, and functional outcomes among participants.

Participation in this study will last 26 weeks. Screening will include a questionnaire and an x-ray of the affected thumb. Eligible participants will then be randomly assigned to one of three treatments: two hyaluronan injections, one corticosteroid injection plus one local anesthetic injection, or two local anesthetic injections. Participants will receive the injections at the base of their thumb, and the first injection will be followed by the second injection a week later. There will be five study visits that will occur at baseline and Weeks 2, 4, 12, and 26. All study visits will include questionnaires, and except for the Week 2 study visit, they will also include an examination and evaluation of the affected thumb. Photographs of the thumb will be taken at baseline. The injections will occur at baseline and Week 2. At Weeks 8 and 20, questionnaires will be mailed to participants for them to complete. Upon completing the study, participants will have the option of receiving continued treatment with another round of hyaluronic injections.

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Study of Hyaluronan (Synvisc) for the Treatment of Osteoarthritis in the Thumb: Randomized Control Trial
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Bupivicaine (local anesthetic)	Drug: Bupivicaine (local anesthesia injection); 1 ml of bupivicaine 0.5% injected once a week for 2 weeks
Active Comparator: 2 Corticosteroid (trimcinolone (Kenalog) 40 mg)	Drug: Kenalog (triamcinolone; corticosteroid injection); 1 ml (40mg) of triamcinolone (Kenalog) injected the first week, followed by a placebo injection of 1 ml 0.5% bupivacaine the second week; Kenalog is a non-suspension steroid preparation and is less likely to cause post-injection flares than a suspension preparation
Experimental: 3 Synvisc	Drug: Synvisc (Hylan G-F20; hyaluronan injection); 1 ml of hyaluronan (Synvisc) injected once a week for 2 consecutive weeks; Other Names: Synvisc, Hyalgan, Hyaluronic Acid

Outcome Measures

Primary Outcome Measures

1. Pain Visual Analogue Scale (VAS) [Baseline, 26 Weeks]

   Pain intensity measured on a Visual Analog Scale with scores ranging from 0 to 100, with 100 = severe pain.

Secondary Outcome Measures

1. Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire [Baseline, 26 Weeks]

   Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire measures degree of disability on a scale of 0 to 100, with a higher score indicating greater disability.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 95 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Presence of osteophytes or sclerosis at the carpometacarpal (CMC) joint

• Complaint of unacceptable pain despite modification of activity and a therapeutic dose of nonsteroidal anti-inflammatory drugs (NSAIDS), if tolerated

• If bilateral disease, only the most severely involved hand (as defined by the visual analog scale [VAS] for pain) will be entered in the study

• Able to follow instructions and complete questionnaires

• Failed conservative therapy with NSAIDS or COX-2 inhibitors

• Unable to tolerate COX-2 inhibitors

Exclusion Criteria:

• Previous traumatic dislocation, ligament tear, or fracture of the thumb in the affected hand

• Previous hand surgery on the affected hand

• Known hand comorbidities (e.g., active carpal tunnel syndrome, de Quervains tenosynovitis, etc.)

• Systemic rheumatic disease

• Bleeding diatheses or anti-coagulation

• Allergies to steroids, chicken products, bupivicaine, or adhesive (e.g., double-sided tape)

• Current use of oral or intravenous steroids

• Active systemic malignancies

• Hyaluronan injection in the target CMC joint in the last 6 months

• Steroid or hyaluronan injection in any other joint in the last 6 months

• Insulin dependent diabetes mellitus (IDDM)

• Active infection

• Pain in the index joint that is more than 40 out of 100 on a VAS Pain scale

• End Stage CMC osteoarthritis, equivalent to bone on bone, Kellgren and Lawrence Stage IV

• Grade 3 or 4 Eaton and Litter (E+L) Classification

• E+L 3: Advanced joint distraction, subchondral cysts, and sclerosis

• E+L 4: Involvement of several joint surfaces

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital for Special Surgery	New York	New York	United States	10021

Sponsors and Collaborators

• Hospital for Special Surgery, New York
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Genzyme, a Sanofi Company

Investigators

• Principal Investigator: Lisa A. Mandl, MD, MPH, Hospital for Special Surgery, New York

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hospital for Special Surgery, New York
• ClinicalTrials.gov Identifier: NCT00398866
• Other Study ID Numbers: K23AR050607; K23AR050607; 5K23AR050607-04; 26043
• First Posted: Nov 14, 2006
• Last Update Posted: Jul 7, 2017
• Last Verified: Jul 1, 2017

• Keywords provided by Hospital for Special Surgery, New York: Hyaluronan; Carpometacarpal; Outcomes; Carpometacarpal Joints
• Additional relevant MeSH terms: Osteoarthritis; Triamcinolone; Triamcinolone Acetonide; Bupivacaine; Hyaluronic Acid; Hylan

Study Results

Participant Flow

Recruitment Details	Patients were recruited from the practices of Hospital for Special Surgery (HSS) physicians or were or self-referred. Study information was posted on the HSS website, clinicaltrials.gov, Craig's List and local newspapers. Recruitment occurred between 05/25/2007 and 07/15/2009.
Pre-assignment Detail	396 subjects screened 169 did not meet eligibility criteria 27 declined injection 200 subjects randomized

Arm/Group Title	Bupivicaine	Triamcinolone	Hylan G-F 20
Arm/Group Description	Bupivicaine (local anesthetic) Bupivicaine (local anesthesia injection): 1 ml of bupivicaine 0.5% injected once a week for 2 weeks	Corticosteroid (triamcinolone (Kenalog) 40 mg) Kenalog (triamcinolone; corticosteroid injection): 1 ml (40mg) of triamcinolone (Kenalog) injected the first week, followed by a placebo injection of 1 ml 0.5% bupivacaine the second week; Kenalog is a non-suspension steroid preparation and is less likely to cause post-injection flares than a suspension preparation	Synvisc Synvisc (Hylan G-F20; hyaluronan injection): 1 ml of hyaluronan (Synvisc) injected once a week for 2 consecutive weeks
Period Title: Overall Study
STARTED	66	68	66
COMPLETED	52	60	58
NOT COMPLETED	14	8	8

Baseline Characteristics

Arm/Group Title	Bupivicaine	Triamcinolone	Hylan G-F 20	Total
Arm/Group Description	Bupivicaine (local anesthetic) Bupivicaine (local anesthesia injection): 1 ml of bupivicaine 0.5% injected once a week for 2 weeks	Corticosteroid (trimcinolone (Kenalog) 40 mg) Kenalog (triamcinolone; corticosteroid injection): 1 ml (40mg) of triamcinolone (Kenalog) injected the first week, followed by a placebo injection of 1 ml 0.5% bupivacaine the second week; Kenalog is a non-suspension steroid preparation and is less likely to cause post-injection flares than a suspension preparation	Synvisc Synvisc (Hylan G-F20; hyaluronan injection): 1 ml of hyaluronan (Synvisc) injected once a week for 2 consecutive weeks	Total of all reporting groups
Overall Participants	66	68	66	200
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.3 (9.3)	66.6 (8.4)	67.1 (10.1)	66.7 (9.3)
Sex/Gender, Customized (Count of Participants)
Female	50 75.8%	40 58.8%	45 68.2%	135 67.5%
Male	16 24.2%	28 41.2%	20 30.3%	64 32%
No data	0 0%	0 0%	1 1.5%	1 0.5%
Race/Ethnicity, Customized (Count of Participants)
White	58 87.9%	61 89.7%	61 92.4%	180 90%
Other	8 12.1%	7 10.3%	4 6.1%	19 9.5%
No data	0 0%	0 0%	1 1.5%	1 0.5%

Outcome Measures

1. Primary Outcome

Title	Pain Visual Analogue Scale (VAS)
Description	Pain intensity measured on a Visual Analog Scale with scores ranging from 0 to 100, with 100 = severe pain.
Time Frame	Baseline, 26 Weeks

Outcome Measure Data

Analysis Population Description

Patients who completed follow-up through 26 weeks

Arm/Group Title	Bupivicaine	Triamcinolone	Hylan G-F 20
Arm/Group Description	Bupivicaine (local anesthetic) Bupivicaine (local anesthesia injection): 1 ml of bupivicaine 0.5% injected once a week for 2 weeks	Corticosteroid (trimcinolone (Kenalog) 40 mg) Kenalog (triamcinolone; corticosteroid injection): 1 ml (40mg) of triamcinolone (Kenalog) injected the first week, followed by a placebo injection of 1 ml 0.5% bupivacaine the second week; Kenalog is a non-suspension steroid preparation and is less likely to cause post-injection flares than a suspension preparation	Synvisc Synvisc (Hylan G-F20; hyaluronan injection): 1 ml of hyaluronan (Synvisc) injected once a week for 2 consecutive weeks
Measure Participants	61	65	62
Pain VAS at Baseline	57.1 (20.1)	63.2 (20.2)	60.7 (19.3)
Pain VAS at 26 weeks	42.9 (26.5)	50.1 (29.4)	49.8 (26.3)

2. Secondary Outcome

Title	Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire
Description	Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire measures degree of disability on a scale of 0 to 100, with a higher score indicating greater disability.
Time Frame	Baseline, 26 Weeks

Outcome Measure Data

Analysis Population Description

Patients who completed follow-up through 26 weeks

Arm/Group Title	Bupivicaine	Triamcinolone	Hylan G-F 20
Arm/Group Description	Bupivicaine (local anesthetic) Bupivicaine (local anesthesia injection): 1 ml of bupivicaine 0.5% injected once a week for 2 weeks	Corticosteroid (triamcinolone (Kenalog) 40 mg) Kenalog (triamcinolone; corticosteroid injection): 1 ml (40mg) of triamcinolone (Kenalog) injected the first week, followed by a placebo injection of 1 ml 0.5% bupivacaine the second week; Kenalog is a non-suspension steroid preparation and is less likely to cause post-injection flares than a suspension preparation	Synvisc Synvisc (Hylan G-F20; hyaluronan injection): 1 ml of hyaluronan (Synvisc) injected once a week for 2 consecutive weeks
Measure Participants	61	65	62
DASH at Baseline	25.7 (17.1)	28.9 (17.9)	28.8 (17.3)
Dash at 26 Weeks	24.2 (17.4)	27.0 (18.0)	26.1 (19.0)

Adverse Events

Arm/Group Title	Bupivicaine		Triamcinolone		Hylan G-F 20
Arm/Group Description	Bupivicaine (local anesthetic) Bupivicaine (local anesthesia injection): 1 ml of bupivicaine 0.5% injected once a week for 2 weeks		Corticosteroid (triamcinolone (Kenalog) 40 mg) Kenalog (triamcinolone; corticosteroid injection): 1 ml (40mg) of triamcinolone (Kenalog) injected the first week, followed by a placebo injection of 1 ml 0.5% bupivacaine the second week; Kenalog is a non-suspension steroid preparation and is less likely to cause post-injection flares than a suspension preparation		Synvisc Synvisc (Hylan G-F20; hyaluronan injection): 1 ml of hyaluronan (Synvisc) injected once a week for 2 consecutive weeks
All Cause Mortality
	Bupivicaine		Triamcinolone		Hylan G-F 20
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Bupivicaine		Triamcinolone		Hylan G-F 20
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/66 (1.5%)		0/68 (0%)		2/66 (3%)
Cardiac disorders
Mitral Valve Surgery	0/66 (0%)	0	0/68 (0%)	0	1/66 (1.5%)	1
Gastrointestinal disorders
Emergency Cholecystecomy	0/66 (0%)	0	0/68 (0%)	0	1/66 (1.5%)	1
Injury, poisoning and procedural complications
Fall--hand injury	1/66 (1.5%)	1	0/68 (0%)	0	0/66 (0%)	0
Other (Not Including Serious) Adverse Events
	Bupivicaine		Triamcinolone		Hylan G-F 20
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/66 (3%)		10/68 (14.7%)		3/66 (4.5%)
Immune system disorders
Positive ANA Test (Previous status unknown)	0/66 (0%)	0	1/68 (1.5%)	1	0/66 (0%)	0
Musculoskeletal and connective tissue disorders
Pain, Swelling, or Numbness in Hand	2/66 (3%)	2	3/68 (4.4%)	3	2/66 (3%)	2
Skin and subcutaneous tissue disorders
Skin Atrophy or Depigmentation	0/66 (0%)	0	4/68 (5.9%)	4	0/66 (0%)	0
Skin and Nail Abnormalities	0/66 (0%)	0	2/68 (2.9%)	2	1/66 (1.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.