SYNVISC-ONE: Synvisc-One for Younger, Active Patients With Osteoarthritis

• Sponsor: Anthony Luke (Other)
• Overall Status: Completed
• CT.gov ID: NCT01625013
• Collaborator: (none)
• Enrollment: 51
• Location: 1
• Arm: 1
• Actual Duration (Months): 93.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study aims to study use of viscosupplementation as a treatment of pain for young individuals who are active. Typically viscosupplementation is considered an intervention for knee osteoarthritis often for older patients who are less active. Many young active patients can also develop knee osteoarthritis after trauma or surgery or for congenital reasons. Treatment of these patients commonly are steroid injections which have more biologically detrimental effects for cartilage compared to viscosupplementation Synvisc One injections which are a single injection will be used to determine effectiveness of reducing pain and maintaining an active healthy lifestyle for younger patients aged 30-50 years old.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis	Device: Synvisc-One (G-F 20)	N/A

Detailed Description

This study will be an open label longitudinal cohort study with natural history over 3 years. Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be entered into the study. Subjects enrolled in the cohort will have baseline functional testing performed including a motion gait analysis, 12 minute walk test, and 3-day accelerometer data. Subjects will receive a single 6 mL intra-articular injection of hylan G-F 20 in the target knee at baseline. All ongoing treatments will be monitored at 6 month intervals over the 3 year duration of the study. Patients can receive any other conservative treatments (e.g., oral medications, physical or other therapy, acupuncture, etc., except other injection treatments) and current treatments will be documented during each patient encounter. An initial injection of hylan G-F 20 will be injected in the symptomatic knee using a standard supine lateral approach using a 20 gauge needle. A face to face follow up visit will be carried out 6 months after first injection with additional face to face meetings every 6 months thereafter unless the subject requires an additional injection of hylan G-F 20. Hylan G-F 20 treatments can be administered up to three times each year during the study duration. After each injection, follow up measures will be carried out using secure e-mail or phone contact at 6 weeks, 12 weeks, 18 weeks after each in-office evaluation or injection. Follow up will consist of WOMAC, Lysholm score, and Tegner score. Patients may return for retreatment of hylan G-F 20 if symptoms recur after at least 4 months following their previous injection and they meet the inclusion criteria with pain levels of WOMAC A1, C8, C9, C10 and/or C23 equaling 2 or more. Patients requiring three injections of hylan G-F 20 in 4 months or less will be allowed to exit the cohort after their six-month follow up following the third injection. Otherwise, patients will be followed until they reach the 3 year follow up, or drop out for other injection treatments or surgical treatment. Therefore, patients would potentially be able to receive up to 9 injections during the 3 year study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Long-Term Management of "Younger, Active" Patients With Pain From Early Knee Osteoarthritis With Synvisc-One (Hylan G-F 20)
• Actual Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Oct 2, 2017
• Actual Study Completion Date: Aug 7, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Synvisc-One

Device: Synvisc-One (G-F 20); Synvisc G-F 20 will be injected in the symptomatic knee using a standard supine lateral approach using a 20-gauge needle. Patients will be treated at baseline and followed out to three years. Patients may return for retreatment as early as 4 months post their prior injection if they meet the retreatment criteria pain levels for Worst Knee Pain. If the subjects need another injection, the follow-up cycle will restart at Visit 1 and the subject will be seen every 6 months and followed-up for 3 years.

Outcome Measures

Primary Outcome Measures

1. "Worst Knee Pain" Likert Scale (0-10) Reported on Survey [26 weeks after injection at baseline]

   Worst Knee Pain Scores were measured using a "Worst Knee Pain" Likert scale, the score ranges from 0-10, zero indicating no pain and 10 indicating the worst pain. Patient Acceptable Symptom State (PASS) is a "Worst Knee Pain" reported score of less than 4 to be "positive". Patient Acceptable Symptom State (PASS) is the highest level of symptom beyond which patients consider themselves well. Minimum Clinical Important Improvement (MCII) is improvement at any time in the 26 week time frame that "Worst Knee Pain" is reported at 2 points less than baseline.

Secondary Outcome Measures

1. Patient Acceptable Symptom Score (The Effect of Repeated Treatments) [26 weeks post-injection Number 2, an average of 52 weeks]

   Though symptoms can be improved for periods up to 6 months, pain symptoms can recur. The effect of repeated treatments of hylan G-F 20 will be studied with the Patient Acceptable Symptom Score less than 4/10 for the reported Worst Knee Pain score on follow up surveys. Worst Knee Pain Scores were measured using a "Worst Knee Pain" Likert scale, the score ranges from 0-10, zero indicating no pain and 10 indicating the worst pain. Patient Acceptable Symptom State (PASS) is a "Worst Knee Pain" reported score of less than 4 to be "positive". Patient Acceptable Symptom State (PASS) is the highest level of symptom beyond which patients consider themselves well.

2. Minimal Clinical Important Improvement (The Effect of Repeated Injections) [up to 15 months (within 3 months from the second Synvisc One injection)]

   Though symptoms can be improved for periods up to 6 months, pain symptoms can recur. The effect of repeated treatments of hylan G-F 20 will be studied with the Minimal Clinical Important Improvement less than 2 points from baseline on a 10-point likert scale for the reported Worst Knee Pain score on any follow up survey within 3 months. Worst Knee Pain Scores were measured using a "Worst Knee Pain" Likert scale, the score ranges from 0-10, zero indicating no pain and 10 indicating the worst pain. Patients can reinject after 4 months.

3. Identify the Effects of Treatment on Activity Levels [26 weeks post-injection at baseline through 3 years post-injection]

   To identify the effects of treatment with hylan G-F 20 on activity levels (using objective activity measures utilizing accelerometer and Physical Activity Enjoyment Scale (PACES) and quality of life scores (WOMAC, SF-12) comparing baseline to treatment at 3 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female patients aged 30-50 years

• History of symptomatic unilateral primary or secondary knee OA for more than 6 months

• Signed written informed consent

• Radiographic evidence of Kellgren-Lawrence Grade I or II OA of the target knee

• Body Mass Index (BMI) < 30 kg/m2

• Activity criteria (Tegner score > 3)

• Continued target knee OA pain despite conservative treatment ≥ 3 months (e.g., weight reduction, physical therapy, analgesics)

• Willing to withhold intake of NSAIDs (including COX-2 inhibitors) and analgesics, for a washout period of minimum 3 days up to 21 days prior to baseline visit (depending on medication)

• Willing to discontinue prohibited treatments and medications throughout study period

Baseline inclusion criteria

• Completed OA medication washout period

• Target knee pain 4-8 (0-10 NRS) during most painful knee movement (Worst Knee Pain)

• If female, must have had a negative urine pregnancy test and used a medically acceptable form of contraception for at least 1 month prior to baseline and agree to continued use of contraception for the duration of the study. Otherwise, females must be surgically sterile, or postmenopausal (as documented in medical history) for at least 1 year. The fetal safety profile for G-F 20 is unknown. Pregnancy will affect the individual's regular activity levels. Females who become pregnant during the study will be excluded from the study. Subjects who become pregnant will be followed up by telephone every 3 months to check for any adverse effects. They will also be recommended to follow routine obstetric visits. Males should be able to father children as it has no expected effects on activity levels.

Exclusion Criteria:

• Known allergy to hylan G-F 20 or any of its components, or to avian proteins, eggs, feathers, down, or poultry

• Clinically apparent tense effusion or other acute inflammation of the target knee at baseline

• History of target knee viscosupplementation treatment

• History of major surgery for OA in target knee including arthroplasty or tibial osteotomy

• Arthroscopic surgery or intraarticular steroid injection in target knee within six months of baseline visit

• Significant (as judged by the Investigator) alignment deformity of target knee

• Ipsilateral symptomatic OA of hip or ankle; contralateral symptomatic OA of hip, knee, or ankle

History of:

• Septic OA of any joint

• Inflammatory arthropathy such as RA, gout, pseudogout, lupus, crystalline inflammatory arthropathy

• Active infection of lower extremity

• Known significant acute and/or concurrent medical disease including, but not limited to current malignancy, history of transplant surgery, congestive heart failure, significant unstable cardiovascular disease, renal hepatic pulmonary, endocrine, metabolic, or GI condition

• Any known contraindication to acetaminophen

• Venous or lymphatic stasis in either leg

• Peripheral vascular disease

• Patient has been prescribed chronic opioid analgesics at time of baseline visit

• Concurrent multi-system or multi-limb trauma

• Patient plans to become pregnant during study period

• Patient plans to move significantly out of area, have surgery, or initiate or cease other OA treatments

• Knee pain improves during washout period

• Workman's Comp patient

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California	San Francisco	California	United States	94158

Sponsors and Collaborators

• Anthony Luke

Investigators

• Principal Investigator: Anthony Luke, MD, University of California, San Francisco

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 17, 2012

More Information

Publications

None provided.

• Responsible Party: Anthony Luke, Associate Professor of Clinical Orthopaedic Surgery, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT01625013
• Other Study ID Numbers: UCSF-SYNVISC-ONE 001
• First Posted: Jun 21, 2012
• Last Update Posted: May 7, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by Anthony Luke, Associate Professor of Clinical Orthopaedic Surgery, University of California, San Francisco: osteoarthritis; viscosupplementation; Active; Knee; Synvisc-One
• Additional relevant MeSH terms: Osteoarthritis; Hylan

Study Results

Participant Flow

Arm/Group Title	Synvisc-One
Arm/Group Description	Synvisc-One (G-F 20): Synvisc G-F 20 will be injected in the symptomatic knee using a standard supine lateral approach using a 20-gauge needle. Patients will be treated at baseline and followed out to three years. Patients may return for retreatment as early as 4 months post their prior injection if they meet the retreatment criteria pain levels for Worst Knee Pain. If the subjects need another injection, the follow-up cycle will restart at Visit 1 and the subject will be seen every 6 months and followed-up for 3 years.
Period Title: Overall Study
STARTED	51
COMPLETED	48
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Synvisc-One
Arm/Group Description	Synvisc-One (G-F 20): Synvisc G-F 20 will be injected in the symptomatic knee using a standard supine lateral approach using a 20-gauge needle. Patients will be treated at baseline and followed out to three years. Patients may return for retreatment as early as 4 months post their prior injection if they meet the retreatment criteria pain levels for Worst Knee Pain. If the subjects need another injection, the follow-up cycle will restart at Visit 1 and the subject will be seen every 6 months and followed-up for 3 years.
Overall Participants	51
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.2 (4.7)
Sex: Female, Male (Count of Participants)
Female	19 37.3%
Male	32 62.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	5 9.8%
Native Hawaiian or Other Pacific Islander	1 2%
Black or African American	2 3.9%
White	32 62.7%
More than one race	0 0%
Unknown or Not Reported	11 21.6%

Outcome Measures

1. Primary Outcome

Title	"Worst Knee Pain" Likert Scale (0-10) Reported on Survey
Description	Worst Knee Pain Scores were measured using a "Worst Knee Pain" Likert scale, the score ranges from 0-10, zero indicating no pain and 10 indicating the worst pain. Patient Acceptable Symptom State (PASS) is a "Worst Knee Pain" reported score of less than 4 to be "positive". Patient Acceptable Symptom State (PASS) is the highest level of symptom beyond which patients consider themselves well. Minimum Clinical Important Improvement (MCII) is improvement at any time in the 26 week time frame that "Worst Knee Pain" is reported at 2 points less than baseline.
Time Frame	26 weeks after injection at baseline

Outcome Measure Data

Analysis Population Description

Patients at 26 weeks post-injection Number 1

Arm/Group Title	Synvisc-One
Arm/Group Description	Synvisc-One (G-F 20): Synvisc G-F 20 will be injected in the symptomatic knee using a standard supine lateral approach using a 20-gauge needle. Patients will be treated at baseline and followed out to three years. Patients may return for retreatment as early as 4 months post their prior injection if they meet the retreatment criteria pain levels for Worst Knee Pain. If the subjects need another injection, the follow-up cycle will restart at Visit 1 and the subject will be seen every 6 months and followed-up for 3 years.
Measure Participants	43
Patient Acceptable Symptom State (PASS)	25 49%
Minimum Clinical Important Improvement (MCII)	35 68.6%

2. Secondary Outcome

Title	Patient Acceptable Symptom Score (The Effect of Repeated Treatments)
Description	Though symptoms can be improved for periods up to 6 months, pain symptoms can recur. The effect of repeated treatments of hylan G-F 20 will be studied with the Patient Acceptable Symptom Score less than 4/10 for the reported Worst Knee Pain score on follow up surveys. Worst Knee Pain Scores were measured using a "Worst Knee Pain" Likert scale, the score ranges from 0-10, zero indicating no pain and 10 indicating the worst pain. Patient Acceptable Symptom State (PASS) is a "Worst Knee Pain" reported score of less than 4 to be "positive". Patient Acceptable Symptom State (PASS) is the highest level of symptom beyond which patients consider themselves well.
Time Frame	26 weeks post-injection Number 2, an average of 52 weeks

Outcome Measure Data

Analysis Population Description

Patients receiving Synvisc One injection Number 2

Arm/Group Title	Synvisc-One Second Injection
Arm/Group Description	Synvisc-One (G-F 20): Synvisc G-F 20 will be injected a second time in the symptomatic knee using a standard supine lateral approach using a 20-gauge needle. Patients will be treated at baseline and followed out until three years from their first injection. Patients may return for retreatment as early as 4 months post their prior injection if they meet the retreatment criteria pain levels for Worst Knee Pain. If the subjects need another injection, the follow-up cycle will restart at Visit 1 and the subject will be seen every 6 months and followed-up for a total of 3 years.
Measure Participants	37
Patient Acceptable Symptom State < 4/10 worst knee pain	0 0%
Patient Acceptable Symptom State > 4/10	18 35.3%
Missing Data	19 37.3%

3. Secondary Outcome

Title	Minimal Clinical Important Improvement (The Effect of Repeated Injections)
Description	Though symptoms can be improved for periods up to 6 months, pain symptoms can recur. The effect of repeated treatments of hylan G-F 20 will be studied with the Minimal Clinical Important Improvement less than 2 points from baseline on a 10-point likert scale for the reported Worst Knee Pain score on any follow up survey within 3 months. Worst Knee Pain Scores were measured using a "Worst Knee Pain" Likert scale, the score ranges from 0-10, zero indicating no pain and 10 indicating the worst pain. Patients can reinject after 4 months.
Time Frame	up to 15 months (within 3 months from the second Synvisc One injection)

Outcome Measure Data

Analysis Population Description

Patients receiving Synvisc One injection Number 2

Arm/Group Title	Synvisc-One Second Injection
Arm/Group Description	Synvisc-One (G-F 20): Synvisc G-F 20 will be injected a second time in the symptomatic knee using a standard supine lateral approach using a 20-gauge needle. Patients will be treated at baseline and followed out until three years from their first injection. Patients may return for retreatment as early as 4 months post their prior injection if they meet the retreatment criteria pain levels for Worst Knee Pain. If the subjects need another injection, the follow-up cycle will restart at Visit 1 and the subject will be seen every 6 months and followed-up for a total of 3 years.
Measure Participants	37
Minimal Clinical Important Improvement more than 2 points improvement from baseline	10 19.6%
MCII less than 2 points improvement from baseline	12 23.5%
Missing Data	15 29.4%

4. Secondary Outcome

Title	Identify the Effects of Treatment on Activity Levels
Description	To identify the effects of treatment with hylan G-F 20 on activity levels (using objective activity measures utilizing accelerometer and Physical Activity Enjoyment Scale (PACES) and quality of life scores (WOMAC, SF-12) comparing baseline to treatment at 3 months.
Time Frame	26 weeks post-injection at baseline through 3 years post-injection

Outcome Measure Data

Analysis Population Description

The minimal data collected are invalid due to end user error and inaccurate data collection practices, therefore no valid data exist to report.

Arm/Group Title	Synvisc-One Second Injection
Arm/Group Description	Synvisc-One (G-F 20): Synvisc G-F 20 will be injected a second time in the symptomatic knee using a standard supine lateral approach using a 20-gauge needle. Patients will be treated at baseline and followed out until three years from their first injection. Patients may return for retreatment as early as 4 months post their prior injection if they meet the retreatment criteria pain levels for Worst Knee Pain. If the subjects need another injection, the follow-up cycle will restart at Visit 1 and the subject will be seen every 6 months and followed-up for a total of 3 years.
Measure Participants	0

Adverse Events

Time Frame	Adverse event data was collected at 6, 12, and 18 weeks after each injection/clinic visit, up to 3 years for each participant.
Arm/Group Title	Synvisc-One
Arm/Group Description	Synvisc-One (G-F 20): Synvisc G-F 20 will be injected in the symptomatic knee using a standard supine lateral approach using a 20-gauge needle. Patients will be treated at baseline and followed out to three years. Patients may return for retreatment as early as 4 months post their prior injection if they meet the retreatment criteria pain levels for Worst Knee Pain. If the subjects need another injection, the follow-up cycle will restart at Visit 1 and the subject will be seen every 6 months and followed-up for 3 years.
All Cause Mortality
	Synvisc-One
	Affected / at Risk (%)	# Events
Total	0/51 (0%)
Serious Adverse Events
	Synvisc-One
	Affected / at Risk (%)	# Events
Total	0/51 (0%)
Other (Not Including Serious) Adverse Events
	Synvisc-One
	Affected / at Risk (%)	# Events
Total	29/51 (56.9%)
Musculoskeletal and connective tissue disorders
Severe Swelling, Pain, and/or Stiffness	27/51 (52.9%)
Reinjury	2/51 (3.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.