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

A Phase I/II Study Evaluating the Preliminary Safety and Efficacy of Treprostinil (Remodulin®) In Reducing Ischemia-Reperfusion Injury During De Novo Adult Kidney Transplantation

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.

Study Overview

• Status: Recruiting
• Conditions: Ischemia Reperfusion Injury; Delayed Graft Function
• Intervention / Treatment: Drug: Treprostinil

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Reginald Y Gohh, MD; Phone Number: 401-444-3284; Email: RGohh@Lifespan.org
• Study Contact Backup: Name: Nisanne Ghonem, PharmD, PhD; Phone Number: 401-874-4805; Email: nghonem@uri.edu

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
      • Contact: Reginald Y Gohh, MD; Phone Number: 401-444-3284; Email: RGohh@Lifespan.org
      • Contact: Nisanne Ghonem, PharmD, PhD; Phone Number: 401-874-4805; Email: nghonem@uri.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: 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.; Other Names: Remodulin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum creatinine (SCr)	Primary efficacy assessment will include the cGFR using SCr during the first seven days post transplantation.	Day 1-7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
INR	biochemical end point	Day 7
Urine output	biochemical end point	Day 7
Primary graft non-function; kidney failure	dialysis, death or re-transplantation	Day 30
Delayed graft function	use of dialysis	Day 30

Collaborators and Investigators

• Sponsor: Rhode Island Hospital
• Collaborators: United Therapeutics; University of Rhode Island

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2020
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 14, 2019
• First Submitted That Met QC Criteria: June 28, 2019
• First Posted (Actual): July 2, 2019

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 18, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: kidney transplantation; Ischemia-reperfusion injury; prostacyclin; delayed graft function; treprostinil
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Ischemia; Wounds and Injuries; Reperfusion Injury; Delayed Graft Function; Antihypertensive Agents; Treprostinil
• Other Study ID Numbers: 974570-5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes