The MONOVISC Hip Osteoarthritis Study

• Sponsor: DePuy Mitek (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02698865
• Collaborator: (none)
• Enrollment: 220
• Locations: 27
• Arms: 2
• Actual Duration (Months): 41.7
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is being done to determine the effectiveness of MONOVISC for the relief of pain and symptoms of osteoarthritis of the hip. Specifically, the study will determine if MONOVISC is more effective than a placebo treatment when delivered as intra-articular injections (injected directly into the hip joint). In this case, the placebo will be a dilute solution of salt water (saline).

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis of the Hip	Device: MONOVISC; Device: Saline	Phase 3

Detailed Description

The primary objective of this study is determine whether two intra-articular injections of MONOVISC, separated by 1 month, are superior to two intra-articular injections of physiologic saline, separated by 1 month, in relieving hip osteoarthritis pain, as determined by reduction in walking pain change from baseline.

Study Design

• Study Type: Interventional
• Actual Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pivotal Study Comparing Two Injections of MONOVISC to Two Injections of Saline in Patients With Osteoarthritis of the Hip
• Actual Study Start Date: Jan 1, 2016
• Actual Primary Completion Date: Mar 15, 2019
• Actual Study Completion Date: Jun 24, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MONOVISC MONOVISC High Molecular Weight Hyaluronan	Device: MONOVISC; Two (2) intra-articular injections of 4 ml MONOVISC, separated by 1 month, delivered under image guidance (ultrasound or fluoroscopy)
Placebo Comparator: Saline Physiologic saline	Device: Saline; Two (2) intra-articular injections of 4 ml saline, separated by 1 month, delivered under image guidance (ultrasound or fluoroscopy)

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Walking Pain as Measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC) A1 Score at Day 180 [Baseline and Day 180]

   The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is widely used in the evaluation of Hip and Knee Osteoarthritis. Walking Pain Score is measured by question A1 on the WOMAC 3.1 Index. The WOMAC questionnaire used in this study was administered in the Numerical rating scale (NRS) format. Question A1 on the WOMAC 3.1 Index measures the amount of pain that a participant has when walking on a flat surface. It is one question that is collected on a scale from 0 to 10 where a score of 0 indicates no pain and a score of 10 indicates extreme pain.

Secondary Outcome Measures

1. Change From Baseline in Walking Pain as Measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC) A1 Score at Day 14, 28, 60 and 120 [Baseline, Day 14, 28, 60 and 120]

   The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is widely used in the evaluation of Hip and Knee Osteoarthritis. Walking Pain Score is measured by question A1 on the WOMAC 3.1 Index. The WOMAC questionnaire used in this study was administered in the Numerical rating scale (NRS) format. Question A1 on the WOMAC 3.1 Index measures the amount of pain that a participant has when walking on a flat surface. It is one question that is collected on a scale from 0 to 10 where a score of 0 indicates no pain and a score of 10 indicates extreme pain.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female ≥ 30 years old

• Body Mass Index (BMI) ≤ 35

• Clinical or radiographic diagnosis of hip osteoarthritis in the target hip, with a Kellgren-Lawrence (K/L) grade of 2 or 3.

• Walking pain NRS ≥ 4 and ≤ 8.

• Willing to discontinue all pain medications (except rescue medication) for 7 days prior to the first study injection and for the duration of the study.

• Willing to discontinue rescue medication for 48 hours prior to the first study injection.

• Willing to discontinue rescue medication for 48 hours prior to all follow-up visits

• Ability to tolerate acetaminophen (e.g. Tylenol).

• Must be physically and mentally willing and able to comply with pre and post-treatment scheduled clinical and radiographic evaluations

• Must voluntarily sign the Institutional Review Board approved Informed Consent Form.

• Must agree not to initiate cannabis therapy during the trial study period.

Exclusion Criteria:

• Radiographic evidence of osteonecrosis in the target hip

• NRS walking pain ≥ 3 the contralateral hip

• Clinically diagnosed osteoarthritis in either knee resulting in walking pain greater than NRS 5.

• Dependence on external stabilization for walking (e.g. cane, crutches, walker, etc.)

• Pain associated with lower back disorders that cannot be differentiated from target hip pain

• Major dysplasia or congenital abnormality

• Diagnosis of fibromyalgia

• Primary inflammatory arthropathy, or any other condition affecting the joint, including rheumatoid arthritis or gout in the target hip

• Any musculoskeletal condition that could impede efficacy measurement of the target hip

• Any major surgery, arthroplasty, or arthroscopy of the lower extremities in the past 6 months, or planned surgery during the study

• Infection of the injection site area

• Chronic skin disorders that could interfere with injection site evaluation

• Patients with asthma who require systemic use of corticosteroids

• Septic arthritis in any joint in the past 12 weeks

• For all patients: known hypersensitivity to hyaluronan, lidocaine, or acetaminophen

• For patients undergoing fluoroscopic injection guidance: known hypersensitivity to iodine-based fluoroscopic contrast agents, shellfish, or iodine

• Intra-articular steroid injection of the target hip within the last 3 months or hyaluronan injection of the target hip within the last 26 weeks

• Systemic corticosteroids within the last 12 weeks

• Glucosamine and/or chondroitin sulfate within last 4 weeks

• Currently on anticoagulation therapy, including aspirin therapy of > 81 mg/day (e.g. one daily "baby aspirin").

• Uncontrolled diabetes mellitus.

• Pregnant or breast feeding, or plan to be pregnant during the course of the study

• Any significant illness (metastasis of any type) that decreases the probability of the subject's survival to the 26 week endpoint

• Patients unwilling/unable to complete a pain/function and quality of life questionnaires

• Significant trauma to the index hip within 26 weeks of screening

• Is receiving workman's compensation, or is currently involved in litigation relating to hip osteoarthritis

• Is receiving prescription pain medication for conditions unrelated to hip osteoarthritis

• Chronic use of narcotics

• Unwilling to return for follow-up visits as described in this protocol

• Otherwise determined by the investigator to be medically unsuitable for participation in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tucson Orthopedic Institute	Tucson	Arizona	United States	85712
2	CORE Orthopedic Medical Center	Encinitas	California	United States	92024
3	Eisenhower Medical Center/Desert Orthopedic Center	Rancho Mirage	California	United States	92270
4	Southern California Orthopedic Institute	Van Nuys	California	United States	91405
5	University of Colorado - Denver	Denver	Colorado	United States	80111
6	Denver Hip and Knee	Denver	Colorado	United States	80134
7	Center for Arthritis and Rheumatic Diseases	Miami	Florida	United States	33173
8	Integral Rheumatology & Immunology Specialists	Plantation	Florida	United States	33324
9	Emory Sports Complex	Brookhaven	Georgia	United States	30329
10	Iowa Orthopedic Center	Des Moines	Iowa	United States	50314
11	Sports Medicine North	Peabody	Massachusetts	United States	01960
12	MedSport - University of Michigan	Ann Arbor	Michigan	United States	48106
13	Professional Orthopedics	Cherry Hill	New Jersey	United States	08034
14	Hospital for Special Surgery	New York	New York	United States	10021
15	Columbia Medical Center	New York	New York	United States	10032
16	University of North Carolina	Chapel Hill	North Carolina	United States	27599
17	OrthoCarolina Sports Medicine Center	Charlotte	North Carolina	United States	28207
18	Sanford Health	Fargo	North Dakota	United States	58103
19	Cleveland Clinic	Garfield Heights	Ohio	United States	44125
20	Rothman Institute	Media	Pennsylvania	United States	19063
21	Texas Orthopedic Specialists	Bedford	Texas	United States	76021
22	Houston Methodist	Houston	Texas	United States	77030
23	Inov8 Orthopaedics	Houston	Texas	United States	77043
24	San Antonio Orthopaedic Group	San Antonio	Texas	United States	78216
25	University of Virginia	Charlottesville	Virginia	United States	22903
26	National Sports Medicine Institute	Lansdowne Town Center	Virginia	United States	20176
27	OrthoVirginia	Lynchburg	Virginia	United States	24501

Sponsors and Collaborators

• DePuy Mitek

Investigators

• Study Director: Brooks J Story, PhD, DePuy Synthes Mitek Sports Medicine

Study Documents (Full-Text)

• Study Protocol - Oct 30, 2017
• Statistical Analysis Plan - Mar 1, 2016

More Information

Publications

None provided.

• Responsible Party: DePuy Mitek
• ClinicalTrials.gov Identifier: NCT02698865
• Other Study ID Numbers: 15-MVH-01
• First Posted: Mar 4, 2016
• Last Update Posted: Dec 1, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Hip; Hyaluronic Acid

Study Results

Participant Flow

Arm/Group Title	Monovisc	Saline
Arm/Group Description	Participants received the intra-articular injections of 4 mL (milliliter) monovisc high molecular weight hyaluronan as active treatment into the hip joint on Day 1 and then second injection on Day 31.	Participants received the intra-articular injections of 4 mL (milliliter) physiologic saline as control treatment into the hip joint on Day 1 and then second injection on Day 31.
Period Title: Overall Study
STARTED	140	80
Treated	140	80
COMPLETED	105	47
NOT COMPLETED	35	33

Baseline Characteristics

Arm/Group Title	Monovisc	Saline	Total
Arm/Group Description	Participants received the intra-articular injections of 4 mL (milliliter) monovisc high molecular weight hyaluronan as active treatment into the hip joint on Day 1 and then second injection on Day 31.	Participants received the intra-articular injections of 4 mL (milliliter) physiologic saline as control treatment into the hip joint on Day 1 and then second injection on Day 31.	Total of all reporting groups
Overall Participants	140	80	220
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.5 (9.55)	59.4 (10.80)	58.8 (10.01)
Sex: Female, Male (Count of Participants)
Female	84 60%	46 57.5%	130 59.1%
Male	56 40%	34 42.5%	90 40.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	20 14.3%	10 12.5%	30 13.6%
Not Hispanic or Latino	120 85.7%	70 87.5%	190 86.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 0.7%	1 1.3%	2 0.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 4.3%	3 3.8%	9 4.1%
White	133 95%	75 93.8%	208 94.5%
More than one race	0 0%	1 1.3%	1 0.5%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Walking Pain as Measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC) A1 Score at Day 180
Description	The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is widely used in the evaluation of Hip and Knee Osteoarthritis. Walking Pain Score is measured by question A1 on the WOMAC 3.1 Index. The WOMAC questionnaire used in this study was administered in the Numerical rating scale (NRS) format. Question A1 on the WOMAC 3.1 Index measures the amount of pain that a participant has when walking on a flat surface. It is one question that is collected on a scale from 0 to 10 where a score of 0 indicates no pain and a score of 10 indicates extreme pain.
Time Frame	Baseline and Day 180

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (SAS) consists of all randomized participants who were enrolled in the study and received either Monovisc or Saline and were analyzed as per treatment received. Here 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure (OM).

Arm/Group Title	Monovisc	Saline
Arm/Group Description	Participants received the intra-articular injections of 4 mL (milliliter) monovisc high molecular weight hyaluronan as active treatment into the hip joint on Day 1 and then second injection on Day 31.	Participants received the intra-articular injections of 4 mL (milliliter) physiologic saline as control treatment into the hip joint on Day 1 and then second injection on Day 31.
Measure Participants	105	47
Mean (Standard Deviation) [Units on a scale]	-1.75 (2.88)	-1.53 (3.21)

2. Secondary Outcome

Title	Change From Baseline in Walking Pain as Measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC) A1 Score at Day 14, 28, 60 and 120
Description	The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is widely used in the evaluation of Hip and Knee Osteoarthritis. Walking Pain Score is measured by question A1 on the WOMAC 3.1 Index. The WOMAC questionnaire used in this study was administered in the Numerical rating scale (NRS) format. Question A1 on the WOMAC 3.1 Index measures the amount of pain that a participant has when walking on a flat surface. It is one question that is collected on a scale from 0 to 10 where a score of 0 indicates no pain and a score of 10 indicates extreme pain.
Time Frame	Baseline, Day 14, 28, 60 and 120

Outcome Measure Data

Analysis Population Description

SAS consists of all randomized participants who were enrolled in the study and received either Monovisc or Saline and were analyzed as per treatment received. Here 'n'(number analyzed) signifies participants who were evaluable at specified timepoints.

Arm/Group Title	Monovisc	Saline
Arm/Group Description	Participants received the intra-articular injections of 4 mL (milliliter) monovisc high molecular weight hyaluronan as active treatment into the hip joint on Day 1 and then second injection on Day 31.	Participants received the intra-articular injections of 4 mL (milliliter) physiologic saline as control treatment into the hip joint on Day 1 and then second injection on Day 31.
Measure Participants	140	80
Change at Day 14	-1.44 (2.32)	-1.16 (2.14)
Change at Day 28	-1.42 (2.46)	-1.13 (2.19)
Change at Day 60	-1.89 (2.76)	-1.75 (2.31)
Change at Day 120	-1.97 (2.79)	-1.58 (2.8)

Adverse Events

Time Frame	Up to 36 months
Adverse Event Reporting Description	Safety Analysis Set (SAS) consisted of all randomized participants who were enrolled in the study and received either Monovisc or Saline and were analyzed as per treatment received.
Arm/Group Title	Monovisc		Saline
Arm/Group Description	Participants received the intra-articular injections of 4 mL (milliliter) monovisc high molecular weight hyaluronan as active treatment into the hip joint on Day 1 and then second injection on Day 31.		Participants received the intra-articular injections of 4 mL (milliliter) physiologic saline as control treatment into the hip joint on Day 1 and then second injection on Day 31.
All Cause Mortality
	Monovisc		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/140 (0%)		0/80 (0%)
Serious Adverse Events
	Monovisc		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/140 (1.4%)		0/80 (0%)
Cardiac disorders
Mitral Valve Prolapse	1/140 (0.7%)		0/80 (0%)
Surgical and medical procedures
Hip Arthroplasty	1/140 (0.7%)		0/80 (0%)
Other (Not Including Serious) Adverse Events
	Monovisc		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/140 (17.9%)		12/80 (15%)
Musculoskeletal and connective tissue disorders
Arthralgia	25/140 (17.9%)		12/80 (15%)

Limitations/Caveats

No Study limitation was reported for this study.

More Information

Certain Agreements

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

A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.