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

Primary Purpose

Ischemia Reperfusion Injury, Delayed Graft Function

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Treprostinil
Sponsored by
Rhode Island Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Ischemia Reperfusion Injury focused on measuring Ischemia-reperfusion injury, kidney transplantation, prostacyclin, treprostinil, delayed graft function

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Rhode Island HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Trepostinil

Arm Description

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.

Outcomes

Primary Outcome Measures

Serum creatinine (SCr)
Primary efficacy assessment will include the cGFR using SCr during the first seven days post transplantation.

Secondary Outcome Measures

INR
biochemical end point
Urine output
biochemical end point
Primary graft non-function; kidney failure
dialysis, death or re-transplantation
Delayed graft function
use of dialysis

Full Information

First Posted
June 14, 2019
Last Updated
July 18, 2023
Sponsor
Rhode Island Hospital
Collaborators
University of Rhode Island, United Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT04005469
Brief Title
Safety and Efficacy of Treprostinil (Remodulin®) In Reducing Ischemia-Reperfusion Injury During Kidney Transplantation
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 13, 2020 (Actual)
Primary Completion Date
July 1, 2025 (Anticipated)
Study Completion Date
June 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rhode Island Hospital
Collaborators
University of Rhode Island, United Therapeutics

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemia Reperfusion Injury, Delayed Graft Function
Keywords
Ischemia-reperfusion injury, kidney transplantation, prostacyclin, treprostinil, delayed graft function

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Treprostinil will be administered intravenously by a standard 3 + 3 dose-escalation approach. The first three patients will receive a starting rate of 1.25 ng/kg/min and if all three patients safely tolerate the first dose, the next three patients will receive a dose of 2.5 ng/kg/min. If any patients experience side effects, additional patients will receive the previous lower dose. 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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Trepostinil
Arm Type
Experimental
Arm Description
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
Intervention Name(s)
Treprostinil
Other Intervention Name(s)
Remodulin®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Serum creatinine (SCr)
Description
Primary efficacy assessment will include the cGFR using SCr during the first seven days post transplantation.
Time Frame
Day 1-7
Secondary Outcome Measure Information:
Title
INR
Description
biochemical end point
Time Frame
Day 7
Title
Urine output
Description
biochemical end point
Time Frame
Day 7
Title
Primary graft non-function; kidney failure
Description
dialysis, death or re-transplantation
Time Frame
Day 30
Title
Delayed graft function
Description
use of dialysis
Time Frame
Day 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Documentation of a diabetes diagnosis as evidenced by one or more clinical features consistent will be noted for all patients. 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: Under the age of 18 years Difficult venous access BMI > 40 kg/m2 Patients with severe clinical gastroparesis as determined by repeated vomiting Prior GI surgery except for cholecystectomy, appendectomy, or Nissen fundoplication Known or history of inflammatory bowel disease or bezoars History of diverticulitis, diverticular stricture, and other intestinal strictures Be receiving any investigational drug other than treprostinil or participating in any other investigational study Be receiving any prostanoid therapy to treat portopulmonary hypertension Have any known hypersensitivity to prostaglandins, prostacyclin or treprostinil Have had a failed kidney transplant within the previous 180 days Be receiving any non-standard immunosuppression protocol or other non-standard treatment that could affect interpretation of the study results Those with significant cardiovascular disease including treatment with inotropes If female, be pregnant or nursing (confirmed by urine test) 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reginald Y Gohh, MD
Phone
401-444-3284
Email
RGohh@Lifespan.org
First Name & Middle Initial & Last Name or Official Title & Degree
Nisanne Ghonem, PharmD, PhD
Phone
401-874-4805
Email
nghonem@uri.edu
Facility Information:
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Reginald Y Gohh, MD
Phone
401-444-3284
Email
RGohh@Lifespan.org
First Name & Middle Initial & Last Name & Degree
Nisanne Ghonem, PharmD, PhD
Phone
401-874-4805
Email
nghonem@uri.edu

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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