Sirogen for Arteriovenous Fistula Outcomes

(ACCESS2 Trial)

No longer recruiting at 27 trial locations

Overseen By Rakesh Raghubanshi

Age: 65+

Sex: Any

Trial Phase: Phase 3

Sponsor: Vascular Therapies, Inc.

Disqualifiers: Prior AV access, Peritoneal dialysis, Hypersensitivity, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Intraoperative (single dose)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Sirogen (Sirolimus, also known as Rapamune) to determine if it can improve outcomes for individuals receiving an arteriovenous fistula (a connection between an artery and a vein) for dialysis. The trial compares two groups: one receives the Sirogen implant during fistula surgery, while the other undergoes surgery without the implant. The goal is to determine if Sirogen can enhance fistula function for dialysis patients. Suitable candidates are those aged 65 or older, currently on hemodialysis for a year or less, and scheduled for a specific type of fistula surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sirolimus, the main ingredient in the Sirolimus eluting Collagen Implant (SeCI), is generally safe. Studies have found that sirolimus, when taken orally, is well-tolerated by patients and remains safe over time. This indicates that the treatment is likely safe for use in the body.

Further research on similar treatments, such as sirolimus-coated balloons, supports their safety and effectiveness in treating blood vessel issues, including those related to arteriovenous fistulas. These findings provide strong evidence that the Sirolimus eluting Collagen Implant should be safe for participants in the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for improving arteriovenous fistula outcomes, which typically involve surgery alone, the new treatment involves using a Sirolimus-eluting Collagen Implant (SeCI). This implant releases sirolimus, a drug that can help prevent the narrowing or blockage of blood vessels after surgery, which is a common complication. Researchers are excited about this approach because it directly targets the healing process at the surgical site, potentially improving long-term fistula function and reducing the need for additional interventions. This innovative delivery method could offer a significant advancement over current options by enhancing surgical success and patient outcomes.

What evidence suggests that the Sirolimus eluting Collagen implant is effective for arteriovenous fistula outcomes?

This trial will compare outcomes for participants receiving a Sirolimus eluting Collagen Implant (SeCI) with those undergoing arteriovenous fistula surgery alone. Research has shown mixed results for sirolimus in a collagen implant. One study found that 66.8% of patients with a sirolimus implant successfully developed their arteriovenous fistula, crucial for effective dialysis. This was only slightly better than the 63.2% success rate in patients without the implant. In other cases, sirolimus has proven effective for other blood vessel conditions, yielding many positive outcomes. Overall, while sirolimus shows promise in some blood vessel treatments, its success in improving fistula outcomes has varied. ^{3 4 6 7 8}

Who Is on the Research Team?

Sriram Iyer, MD

Principal Investigator

Vascular Therapies, Inc.

Are You a Good Fit for This Trial?

This trial is for people aged 65 or older who have been on hemodialysis for less than a year and are getting a new arteriovenous fistula. It's not for those with previous AV access in the same limb, planned peritoneal dialysis soon, sirolimus or bovine collagen allergies, HIV positive individuals, prisoners, or substance abusers.

Inclusion Criteria

I have had a successful single stage radiocephalic fistula surgery.

I am 65 years old or older.

I have been on hemodialysis for 12 months or less.

Exclusion Criteria

I am scheduled to start peritoneal dialysis within the next 6 months.

I have had a previous surgery for vein access in the same arm where my fistula surgery is planned.

Prisoner, mentally incompetent, and/or current alcohol or drug abuser

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo AV fistula surgery, with the treatment arm receiving the Sirolimus eluting Collagen Implant (SeCI)

Intraoperative (single dose)

Follow-up

Participants are monitored for fistula maturation and safety for one year after surgery

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Sirolimus

Trial Overview The study tests Sirogen—a Sirolimus eluting Collagen implant—given once during surgery to create an arteriovenous fistula used in hemodialysis. The goal is to see if this treatment can prevent complications related to vascular access.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 1 Intervention

Subjects randomized to the treatment arm will undergo AV fistula surgery and will receive the Sirolimus eluting Collagen Implant (SeCI).

Group II: Control Arm Active Control 1 Intervention

Subjects randomized to the control arm will undergo AV fistula surgery alone and will not receive an implant.

Sirolimus is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in European Union as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in Canada as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in Japan as Rapamune for:

• Prevention of organ rejection in kidney transplant patients

Who Is Running the Clinical Trial?

Vascular Therapies, Inc.

Lead Sponsor

Trials

2

Recruited

410+

Published Research Related to This Trial

Sirolimus (rapamycin) is an effective immunosuppressant approved for preventing graft rejection in kidney transplants, with a lower risk of complications compared to other immunosuppressants.

Recent findings suggest that sirolimus may also have potential in treating skin disorders and extending lifespan, making it a promising candidate for addressing age-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sirolimus: a therapeutic advance for dermatologic disease. Peters, T., Traboulsi, D., Tibbles, LA., et al.[2014]

Sirolimus (RAPA) treatment in renal transplant patients significantly increases plasma triglyceride levels and VLDL-apoB100 concentrations due to a reduced catabolic rate of these lipoproteins, rather than increased production.

The study found that RAPA-induced hyperlipidemia is linked to decreased clearance of apoB100-containing lipoproteins, highlighting a metabolic pathway that could be targeted to manage lipid levels in patients undergoing immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of sirolimus on the metabolism of apoB100- containing lipoproteins in renal transplant patients. Hoogeveen, RC., Ballantyne, CM., Pownall, HJ., et al.[2019]

In a study involving 209 kidney transplant recipients in Korea, Rapamune (Sirolimus) demonstrated an acceptable safety profile, with 54.07% of subjects reporting adverse events, most of which were mild and resolved by the end of the study.

The efficacy of Rapamune was notable, with a low incidence of biopsy-proven acute rejection at 2.87% and a high graft survival rate of 99.51%, indicating its effectiveness in preventing kidney allograft rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Rapamune® (Sirolimus) in kidney transplant recipients: results of a prospective post-marketing surveillance study in Korea. Jeon, HJ., Lee, HE., Yang, J.[2019]

The Selution Sustained Limus Release (SLR) sirolimus-coated balloon shows promise for improving the patency of failing arterio-venous fistulas in hemodialysis patients, with a focus on safety and efficacy in a pilot study involving 40 patients.

Pre-clinical studies indicate that the sirolimus coating has prolonged retention in arterial tissue and demonstrates safety with no significant adverse effects, suggesting it may be a viable alternative to existing treatments for conduit stenosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intervention with selution SLR™ Agent Balloon for Endovascular Latent Limus therapy for failing AV Fistulas (ISABELLA) Trial: Protocol for a pilot clinical study and pre-clinical results. Tang, TY., Chong, TT., Yap, CJQ., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34240451/

Efficacy and safety of oral sirolimus for high-flow vascular ... Partial response was observed in eight of the nine patients (88.9%) with high-flow vascular malformation, while worsening was observed in the remaining patient.

2. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-08502-1

Paclitaxel- or sirolimus-coated balloons used for ... The purpose of this trial is to compare the efficacy of additional paclitaxel-coated or sirolimus-coated balloons on outcomes after a plain balloon ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05425056

NCT05425056 | A Study Testing the Use of a Perivascular ... This is a Phase 3, multicenter, randomized, single-blind, controlled, study designed to evaluate the efficacy and safety of the use of the Sirolimus-eluting ...

4. withpower.com withpower.com/trial/phase-3-complication-of-hemodialysis-5-2022-68430

Sirogen for Arteriovenous Fistula Outcomes (ACCESS2 Trial) The efficacy of Rapamune was notable, with a low incidence of biopsy-proven acute rejection at 2.87% and a high graft survival rate of 99.51%, indicating its ...

5. vascularnews.com vascularnews.com/cx-2025-sirolimus-implant-fails-to-meet-fistula-maturation-endpoint-in-access-2-trial/

CX 2025: Sirolimus implant fails to meet fistula maturation ... Inston reported that 66.8% of patients in ACCESS 2's Sirogen arm achieved clinical fistula maturation compared to 63.2% in the control— ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02513303

Trial to Evaluate the Sirolimus-Eluting Collagen Implant on ... The objective of this study is to evaluate efficacy and safety outcomes following use of the Sirolimus-eluting Collagen Implant (SeCI) in subjects undergoing ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10845821/

Sirolimus-coated balloon angioplasty in maintaining the ... It is known that de novo lesions in arteriovenous fistula usually achieve the best patency rates with the first angioplasty. Some studies on paclitaxel drug- ...

8. vascularclinic.sg vascularclinic.sg/wp-content/uploads/2022/06/Endovascular-salvage-of-failing-arterio-venous-fistulas-utilising-sirolimus-eluting-balloons-Six-months-results-from-the-ISABELLA-trial-by-Dr-Tang-Tjun-Yip.pdf

Endovascular-salvage-of-failing-arterio-venous-fistulas- ... Conclusions: Fistuloplasty using the novel Selution SLR™ SEB for dysfunctional AVF circuits seems a safe and effective modality in Asian haemodialysis patients ...