RecruitingPhase 1Phase 2NCT04005469

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


Sponsor

Rhode Island Hospital

Enrollment

20 participants

Start Date

Nov 13, 2020

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria3

  • 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 Criteria15

  • 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

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Interventions

DRUGTreprostinil

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.


Locations(1)

Rhode Island Hospital

Providence, Rhode Island, United States

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NCT04005469


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