Safety and Efficacy of Treprostinil (Remodulin®) In Reducing Ischemia-Reperfusion Injury During Kidney Transplantation

NCT ID: NCT04005469

Last Updated: 2023-07-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-13
• Study Completion Date: 2026-06-30

Brief Summary

The objectives of this study are to test the preliminary safety and efficacy of a two-day peri-operative course of treprostinil in reducing ischemia-reperfusion injury in adult patients receiving a deceased donor kidney transplantation. Treprostinil, a prostacyclin analog, is expected to facilitate the restoration of blood supply to the revascularized kidney graft via its vasodilatory actions, well characterized protective effects, and longer elimination half-life. These properties and actions of treprostinil make it a strong drug candidate to reduce kidney graft dysfunction during kidney transplantation. An anticipated 20 participants undergoing deceased donor kidney transplant will be hospitalized and intensively monitored during an entire two-day Treatment Phase. An IV infusion using a dedicated central venous line will be used to administer treprostinil commencing approximately 2-3 hours before transplantation of the kidney graft and will continue for approximately 48 hours after completion of the transplant surgery. The primary endpoints include the safety and efficacy of treprostinil, with secondary endpoints including the evaluation of both biochemical and clinical endpoints post-transplantation.

Conditions

Ischemia Reperfusion Injury; Delayed Graft Function

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Trepostinil

Treprostinil (Remodulin) will be administered IV by a standard 3 + 3 dose-escalation approach. This dosing model will be followed until a target dose of 15 mg/kg/min is achieved or if it is medically determined that side effects prevent dose escalation. IV infusion will commence approximately 2-3 hours before transplantation of the kidney graft and will continue for approximately 48 hours after completion of surgery, unless hemodynamic changes or tolerability require discontinuation of treprostinil.

Group Type: EXPERIMENTAL

Treprostinil

Intervention Type: DRUG

Treprostinil (Remodulin) will be administered IV by a standard 3 + 3 dose-escalation approach. This dosing model will be followed until a target dose of 15 mg/kg/min is achieved or if it is medically determined that side effects prevent dose escalation. IV infusion will commence approximately 2-3 hours before transplantation of the kidney graft and will continue for approximately 48 hours after completion of surgery, unless hemodynamic changes or tolerability require discontinuation of treprostinil.

Interventions

Treprostinil

Treprostinil (Remodulin) will be administered IV by a standard 3 + 3 dose-escalation approach. This dosing model will be followed until a target dose of 15 mg/kg/min is achieved or if it is medically determined that side effects prevent dose escalation. IV infusion will commence approximately 2-3 hours before transplantation of the kidney graft and will continue for approximately 48 hours after completion of surgery, unless hemodynamic changes or tolerability require discontinuation of treprostinil.

Intervention Type: DRUG

Other Intervention Names

Remodulin®

Eligibility Criteria

Inclusion Criteria

1. Male and female patients who will receive a deceased donor kidney aged 18 to 65 (inclusive) and are currently on the active transplant list at RIH.

2. Documentation of a diabetes diagnosis as evidenced by one or more clinical features consistent will be noted for all patients.

3. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

Exclusion Criteria

1. Under the age of 18 years

2. Difficult venous access

3. BMI > 40 kg/m2

4. Patients with severe clinical gastroparesis as determined by repeated vomiting

5. Prior GI surgery except for cholecystectomy, appendectomy, or Nissen fundoplication

6. Known or history of inflammatory bowel disease or bezoars

7. History of diverticulitis, diverticular stricture, and other intestinal strictures

8. Be receiving any investigational drug other than treprostinil or participating in any other investigational study

9. Be receiving any prostanoid therapy to treat portopulmonary hypertension

10. Have any known hypersensitivity to prostaglandins, prostacyclin or treprostinil

11. Have had a failed kidney transplant within the previous 180 days

12. Be receiving any non-standard immunosuppression protocol or other non-standard treatment that could affect interpretation of the study results

13. Those with significant cardiovascular disease including treatment with inotropes

14. If female, be pregnant or nursing (confirmed by urine test)

15. Presence of a condition or abnormality that in the opinion of the Investigators that would compromise the safety of the patient or the quality of the data

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Rhode Island

OTHER

Sponsor Role: collaborator

United Therapeutics

INDUSTRY

Sponsor Role: collaborator

Rhode Island Hospital

OTHER

Sponsor Role: lead

Responsible Party

Reginald Gohh

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Reginald Y Gohh, MD

Role: CONTACT

RGohh@Lifespan.org

401-444-3284

Nisanne Ghonem, PharmD, PhD

Role: CONTACT

nghonem@uri.edu

401-874-4805

Facility Contacts

Reginald Y Gohh, MD

Role: primary

RGohh@Lifespan.org

401-444-3284

Nisanne Ghonem, PharmD, PhD

Role: backup

nghonem@uri.edu

401-874-4805

Other Identifiers

974570-5

Identifier Type: -

Identifier Source: org_study_id