An Efficacy and Safety Study of SRM003 in the Treatment of Subjects Undergoing Creation of an Arteriovenous Fistula to Facilitate Hemodialysis Access

Arteriovenous Fistula Clinical Trial

Official title:

A Phase 2, Single-blind, Randomized, Controlled, Multi-center Study to Evaluate the Efficacy and Safety of SRM003 (Vascugel®) in Improving the Rate of Arteriovenous Fistula Maturation and Use in Subjects Undergoing Surgery for Creation of an Arteriovenous Fistula for Hemodialysis Access

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01806545
• Other study ID #: AVF01-SRM003
• Status: Completed
• Phase: Phase 2
• Start date: March 26, 2013
• Est. completion date: October 27, 2014

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study to evaluate the efficacy of SRM003 treatment versus participating sites' standard practice treatment in improving the rate of AVF maturation and use in subjects with end-stage renal disease undergoing surgery for creation of an AVF to facilitate hemodialysis access. It is hypothesized that when placed outside the blood vessel, the seeded SRM003 gelatin matrix containing endothelial cells can provide a continuous supply of multiple growth regulatory compounds to the underlying cells within the blood vessel, while being protected from the effects of blood flow in the vessel(s) or complications resulting from being in direct contact with the point of injury.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: October 27, 2014
• Est. primary completion date: October 27, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Subject must be 18 years of age or older at the time of signing and dating informed consent (no upper age limit), can be male or female.

2. Subject who is of child bearing potential must agree to use adequate contraception for 6 months after randomization.

3. Subject must be currently undergoing hemodialysis or anticipating the start of hemodialysis and must require a new permanent, suitable access for the AVF creation in the upper extremity.

4. Subject must have a life expectancy of at least 26 weeks after randomization.

5. Subject must be able to understand and be willing to complete all study requirements.

Exclusion Criteria:

1. Subject is currently on an active organ transplant list from a deceased donor or is undergoing assessment and expects to be placed on the active organ or bone marrow transplant list within the next 26 weeks from surgery, or expects to receive a living donor organ or bone marrow within the next 26 weeks and is unwilling to change transplant list status to "hold" for 3 months after randomization.

2. Subject has had more than 1 access placement surgery (defined as a new access, not a revision) in the target limb.

3. Subject has medical conditions and diseases that may cause non-compliance with the protocol

4. Subject has a known allergy to bovine/porcine products or collagen/gelatin products.

5. Subject has a history of intravenous drug use within 6 months prior to screening

6. Subject is morbidly obese, defined as having a body mass index >40.

7. Pregnant or nursing woman, or plans to become pregnant during the study.

Related Conditions & MeSH terms

• Arteriovenous Fistula
• Fistula

Intervention

Biological:
• SRM003
One time implant (2 SRM003 pieces) on surgery day.

Other:
• Participating Site's standard practice
Subjects will receive sites' standard practice treatment during the surgical procedure.

Locations

Country	Name	City	State
United States	Georgia Regents University	Augusta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	Montefiore Medical Center	Bronx	New York
United States	Fletcher Allen Health Care Renal Service	Burlington	Vermont
United States	Metrolina Nephrology Associates, PA	Charlotte	North Carolina
United States	Erlanger Hospital Pharmacy	Chattanooga	Tennessee
United States	University of Cincinnati Physicians Company	Cincinnati	Ohio
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Renaissance Renal Research Institute, LLC	Detroit	Michigan
United States	Sanford Research/USD-Fargo	Fargo	North Dakota
United States	Ladenheim Dialysis Access Center	Fresno	California
United States	ECU Department of Nephrology and Hypertension	Greenville	North Carolina
United States	Baylor College of Medicine ICTR	Houston	Texas
United States	United Health Services	Johnson City	New York
United States	Clinical Research Consultants, LLC	Kansas City	Missouri
United States	California Institute of Renal Research	La Mesa	California
United States	VA Long Beach Health Care System Pharmacy	Long Beach	California
United States	The Regents University of California Los Angeles	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	Kaiser Permanente Northwest	Milwaukie	Oregon
United States	Nephrology Associates, P.C.	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Ochsner Baptist Medical Center, Clinical Trials Unit	New Orleans	Louisiana
United States	Mount Sinai School of Medicine Lab	New York	New York
United States	Sentara Vascular Specialists	Norfolk	Virginia
United States	SC Nephrology & Hypertension Center, Inc.	Orangeburg	South Carolina
United States	Illinois Kidney Disease & Hypertension Center	Peoria	Illinois
United States	McLaren Northern Michigan Hospital-NISUS Research	Petoskey	Michigan
United States	Delaware Valley Nephrology and Hypertension Associates, PC	Philadelphia	Pennsylvania
United States	Penn Medicine, Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Temple University School of Medicine	Philadelphia	Pennsylvania
United States	Akdhc Medical Research Services	Phoenix	Arizona
United States	Northwest Renal Clinic, Inc.	Portland	Oregon
United States	Sierra Nevada Nephrology Consultants	Reno	Nevada
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	California Institute of Renal Research	San Diego	California
United States	University of California, San Francisco	San Francisco	California
United States	Louisiana State University Health Science Center Shreveport	Shreveport	Louisiana
United States	Providence Hospital, Research Dept.	Southfield	Michigan
United States	Baystate Medical Center Pharmacy	Springfield	Massachusetts
United States	Tampa General Hospital	Tampa	Florida
United States	Toledo Hospital	Toledo	Ohio
United States	Tucson Vascular Consultants	Tucson	Arizona
United States	Wenatchee Valley Medical Center	Wenatchee	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Arteriovenous Fistula (AVF) Maturation by Week 12 Visit Based on Hemodialysis or Color-flow Doppler Ultrasound (CDUS) And Vascular Access Examination	Maturation based on CDUS was assessed in a continuous fashion and was defined by the following criteria: presence of bruit throughout systole and diastole at least 8 centimeters (cm) proximal to the venous anastomosis, blood flow through the outflow vein of at least 500 milliliters (ml) per minute, and a lumen diameter of the outflow vein at least 4 mm. Maturation was determined by CDUS and vascular access examination or by first use of the AVF for hemodialysis based on investigator-reported use. Participants who discontinued prior to the Week 12 visit without assessment of maturity were considered treatment failures.	12 weeks after surgery
Secondary	Percentage of Participants With AVF Maturation by Week 26 Visit Based on Hemodialysis or CDUS And Vascular Access Examination	Maturation based on CDUS was assessed in a continuous fashion and was defined by the following criteria: presence of bruit throughout systole and diastole at least 8 centimeters (cm) proximal to the venous anastomosis, blood flow through the outflow vein of at least 500 milliliters (ml) per minute, and a lumen diameter of the outflow vein at least 4 mm. Maturation was determined by CDUS and vascular access examination or by first use of the AVF for hemodialysis based on investigator-reported use. Participants who discontinued prior to the Week 26 visit without assessment of maturity were considered treatment failures.	26 weeks after surgery
Secondary	Time to AVF Maturation Based on Hemodialysis or CDUS and Vascular Access Examination	Time to AVF maturation was defined as the duration of time (in days) from the date of randomization (AVF creation) to the date of maturation, where the date of maturation corresponds to the earlier of either the date of the first use of the study AVF for hemodialysis as determined by the investigator following discussion with the participant, or the date the AVF meets all of the following 3 criteria as determined through CDUS and vascular access examination: presence of bruit throughout systole and diastole at least 8 centimeters proximal to the venous anastomosis, blood flow through the outflow vein of at least 500 milliliters (ml) per minute, and a lumen diameter of the outflow vein at least 4 mm. Participants who died, underwent a kidney transplant, or were either lost to follow-up or did not mature during the study follow-up were censored at the time of death, time of transplant, or time of last visit, respectively.	Up to 26 weeks after surgery
Secondary	Percentage of Participants With Loss of Unassisted Primary Patency	The time to loss of unassisted primary patency (intervention--free access survival) was defined as the duration of time in days from the date of randomization (AVF creation) until the first date of (a) any intervention designed to establish, maintain, or restore patency; (b) occlusion (commonly due to thrombosis); or (c) access abandonment.	Up to 26 weeks after surgery
Secondary	Percentage of Participants With Loss of Assisted Primary Patency	The time to loss of assisted primary patency (thrombosis--free access survival) was defined as the duration of time in days from the date of randomization (AVF creation) until the first date of (a) occlusion (commonly due to thrombosis) or (b) access abandonment.	Up to 26 weeks after surgery
Secondary	Percentage of Participants With Loss of Secondary Patency	The time to loss of secondary patency (access survival until abandonment) was defined as the duration of time in days from the date of randomization (AVF creation) until the date of access abandonment.	Up to 26 weeks after surgery
Secondary	Change From Week 1 in Average Vascular Access Lumen Diameter Using CDUS	B-mode lumen diameter measurements were obtained in the outflow vein as 3 separate images for each location: at 1, 3, and 5 centimeter into the vein and from the toe of the venous anastomosis. The average of lumen diameter measurements obtained at 1, 3, and 5 cm from the anastomosis was used for this endpoint.	1, 12, and 26 weeks after surgery
Secondary	Percentage of Participants With Clinical Success Based on First Use of The Study AVF For Hemodialysis	Clinical success was defined as the ability to undergo hemodialysis using the AVF. The date of clinical success corresponded to the date of the first use of the study AVF for hemodialysis as determined by the investigator, following discussion with the subject. Clinical success was assessed in a continuous fashion and, once achieved, the AVF was considered a clinical success at that and all subsequent time points. The date of clinical success based on the first use of the AVF for hemodialysis was compared with the dates of each study visit (Week 12 and Week 26); for study visits occurring prior to the date of clinical success based on the first use of the AVF for hemodialysis, the subject was counted as a nonsuccess and for study visits occurring on or after the date of maturation based on the first use of the AVF for hemodialysis, the subject was counted as a success.	12 and 26 weeks after surgery
Secondary	Number of Interventions to Establish, Maintain, or Restore Patency	The total number of interventions to establish, maintain, or restore patency was recorded for each participant.	12 and 26 weeks after surgery