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RUCONEST® as a Therapeutic Strategy to Reduce the Incidence of Delayed Graft Function

Phase 1
Conditions
Kidney Failure
Interventions
Other: Saline Solution
Registration Number
NCT03791476
Lead Sponsor
University of Wisconsin, Madison
Brief Summary

An unmet medical need exists for therapeutic regimens in transplantation that allow immediate postoperative graft function, thereby improving graft survival. Delayed graft function (DGF) after transplantation is the most common complication affecting kidney allographs in the immediate transplant period. The specific aim of this study is to evaluate the effect of recombinant human C1-inhibitor (rhC1INH), as a kidney recipient intra- and post operative treatment strategy to decrease systemic inflammation and decrease the incidence of DGF from donation after cardiac death donors (DCD).

Detailed Description

This is a randomized, single-center double blinded study.

The main objective of this study are to determine the ability of rhC1INH to reduce the incidence and severity of delayed graft function in comparison to placebo in recipients of kidneys after cardio-circulatory determination of death (DCD).

This trial has specifically been designed to evaluate the protective effect of rhC1INH treatment in patients at high risk of developing DGF. The selection of potential donors to be part of this study will be limited to the population of DCD donors which have historically shown a risk of developing DGF ranging between 40-55%. Participation in each group will be randomly assigned. Treatment will be administered by an intra-operative infusion of placebo or rhC1INH (100 Units/kg) IV followed by twice a day infusion of 50 Units/Kg IV for the following 48 hours.

A total of 20 subjects will be divided into 2 groups:

Group 1: Control group: standard recipient management + placebo (0.9% Sodium Chloride IV to equal volume of investigational arm: intraoperatively, and then every 12 hours x 2 = total of 3 doses). treatment (n=10) Group 2: Standard recipient management + 100 U/kg intraoperative followed by 50 U/kg every 12 hours x 2 = total of 3 doses (200 U/kg).

Max dose 8400 units for the initial dose and 4200 units maximum for the second and third doses.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
20
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
rhC1INHrhC1INHIntervention is rhC1INH 100 U/kg intraoperative followed by 50 U/kg every 12 hours x 2 = total of 3 doses (200 U/kg)
Control GroupSaline SolutionIntervention is saline solution placebo (0.9% Sodium Chloride IV to equal volume of investigational arm: intraoperatively, and then every 12 hours x 2 = total of 3 doses)
Primary Outcome Measures
NameTimeMethod
Number of patients that do not meet DGF criteria based on creatinine levels following kidney transplantation from DCD donor who are treated with study drug compared to placeboover a 12 month period

Incidence of delayed graft function in the first 7 days following kidney transplant as defined as the initiation of dialysis in the first 7-days post transplantation and functional DGF as defined as a failure of the serum creatinine to decrease by at least 10% daily on 3 successive days during the first week post transplantation.

Secondary Outcome Measures
NameTimeMethod
Tolerability following drug administration as measured by respiratory rateover a 12 month period

The ability and tolerability to administer the study drug 3 times with appropriate pre and post administration by recording the respiratory rate as breathes per minute

Willingness of participation will be evaluated based on number of potential study candidates (approaches) compared to the number of candidates that enroll in the study likely response ratesover a 12 month period

Enrollment rate of eligible participants

Tolerability following drug administration as measured by temperatureover a 12 month period

The ability and tolerability to administer the study drug 3 times with appropriate pre and post administration by recording temperature in degrees Fahrenheit

Tolerability following drug administration as measured by HR (heart rate)over a 12 month period

The ability and tolerability to administer the study drug 3 times with appropriate pre and post administration by recording heart rate as beats per minute

Tolerability of drug administration as measured by urinary outputover a 12 month period

To assess tolerability, upon administration of the drug, amount of urinary output will be recorded in mL

Incidence of adverse and serious adverse events will be assessed via descriptive statistics methodover a 12 month period

The feasibility of different statistical methods to analyze the incidence of adverse and serious adverse events

Ascertain whether any unexpected toxicities will occur in this patient population according to the Common Toxicity Criteria for Adverse Events (CTCAE) patient populationover a 12 month period

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Tolerability following drug administration as measured by blood pressureover a 12 month period

The ability and tolerability to administer the study drug 3 times with appropriate post administration by recording blood pressure in mmHg

Trial Locations

Locations (1)

University of Wisconsin

🇺🇸

Madison, Wisconsin, United States

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