Intravenous Estrogen in Kidney Transplant Study (PERT)
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|ClinicalTrials.gov Identifier: NCT03663543|
Recruitment Status : Recruiting
First Posted : September 10, 2018
Last Update Posted : June 4, 2020
|Condition or disease||Intervention/treatment||Phase|
|Ischemia Reperfusion Injury||Drug: Conjugated Estrogen Drug: Normal saline||Phase 1 Phase 2|
Ischemia-reperfusion injury (IRI) is a major etiology of organ injury and dysfunction that occurs during transplantation. In renal transplantation, the clinical manifestation of IRI is delayed graft function (DGF), typically defined as a recipient requiring dialysis within the first week after transplant. At present, there are no directed treatments for IRI associated with kidney transplantation and resultant DGF, other than supportive care with dialysis. This represents an unmet clinical need. While dialysis enables the support of patients until DGF resolves, DGF is associated with increased medical costs, increased length of hospital stay, increased rates of readmission to the hospital after transplantation, increased rates of rejection, and decreased graft survival. Therapies to reduce IRI might alleviate clinical complications associated with DGF, reduce costs associated with transplantation, and ease organ shortages by facilitating use of more marginal organs.
Despite acceptance of gender disparities in IRI tolerance in animal systems, attempts to utilize hormonal manipulation in humans to achieve improved IRI tolerance have not been undertaken. In an effort to design such a translation, the investigators investigated if similar gender disparities exist in humans who have undergone kidney transplantation. After review of the United Network for Organ Sharing database, the investigators established that male recipient gender was highly associated with DGF. Then, the investigators demonstrated that manipulation of the pre-ischemic environment with short-term estrogen supplementation in female mice provides protection from renal IRI. As a logical next stop, the investigators propose hormonal manipulation with perioperative administration of intravenous conjugated estrogens as a novel therapeutic strategy to reduce the effect of IRI in female humans undergoing kidney transplantation. The investigators have designed an investigational new drug (IND) late phase I/early phase II prospective, single center, double blind, randomized, placebo-controlled trial to test the safety, feasibility, and efficacy of this therapy. If the administration of peri-operative intravenous administration has a positive impact on the rate of recovery of GFR after renal transplant and the inherent IRI, then this therapy would represent the first treatment for IRI and ultimately might reduce the incidence of DGF. Because DGF after kidney transplantation is associated with inferior transplant outcomes and increased costs,2 a therapy that mitigates the effect of IRI and consequently reduces the incidence of DGF not only might alleviate these complications but could also ease organ shortages by facilitating the use of more marginal organs. Moreover, if estrogen therapy does mitigate IRI in the setting of renal transplantation, it could be applied to other causes of renal IRI including supra-celiac clamping in trauma or vascular surgery or the use of cardiopulmonary bypass in cardiac surgery. Female adult subjects with a diagnosis of end stage renal disease who are dialysis dependent at the time of deceased donor renal transplantation and meet the inclusion and exclusion criteria will be eligible for participation in this study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Parallel: Participants are assigned to one of two or more groups in parallel for the duration of the study|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||The Use of Peri-Operative Intravenous Estrogen for the Mitigation of Ischemia Reperfusion Injury in the Setting of Renal Transplantation|
|Actual Study Start Date :||August 26, 2016|
|Estimated Primary Completion Date :||January 31, 2022|
|Estimated Study Completion Date :||January 31, 2022|
Active Comparator: Active Arm
Participants randomized to the active arm will receive a single infusion of conjugated estrogens at the time of admission if within 8 hours of the expected surgery time or at approximately 8 hours to the expected surgery time if admission is earlier than that. Participants will then receive two daily infusions of conjugated estrogens after transplant given at 8 hours after reperfusion of the transplanted kidney and 24 hours after the first post transplant dose (32 hours after reperfusion of the transplanted kidney).
Drug: Conjugated Estrogen
Dosing of conjugated estrogen will be given pre kidney transplant procedure and twice after reperfusion of the transplanted kidney.
Other Name: Premarin
Placebo Comparator: Placebo Arm
Participants randomized to the placebo arm will receive normal saline (0.9% sodium chloride) at the same rate as the active arm.
Drug: Normal saline
Dosing of normal saline will be given pre kidney transplant procedure and twice after reperfusion of the transplanted kidney.
Other Name: 0.9% sodium chloride
- Glomerular filtration rate (GFR) [ Time Frame: Post-operative day three ]GFR (glomerular filtration rate) as calculated from a DTPA (Diethylenetriamine Pentaacetic Acid, a medication) renal scan.
- Delayed graft function (DGF) [ Time Frame: Immediately post-operative ]Measurement of urine creatinine clearance and serum creatinine.
- Graft Failure [ Time Frame: Post-operative day three and day ninety ]Measurement of serum creatinine.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03663543
|Contact: Mary C Shaw, RNfirstname.lastname@example.org|
|United States, Pennsylvania|
|University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Mary C Shaw, RN 215-614-0528 email@example.com|
|Principal Investigator: Matthew L Levine, MD|
|Principal Investigator:||Matthew Levine, MD, PhD||University of Pennsylvania Health System|