Renaparin® in Kidney Transplantation

Study Overview
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Brief Summary
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This study evaluates the safety and tolerability of Renaparin in adult patients receiving a deceased donor kidney treated ex-vivo with Renaparin prior to transplantation. Half the patient group will receive a kidney treated with Renaparin, while the other half of the patient group will receive a kidney treated with placebo.

Detailed Description
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Kidney transplantation is the last resort for end-stage renal disease (ESRD). A key problem after transplantation is Delayed Graft Function (DGF). Short term, DGF will result in patients being put on dialysis in the immediate time-period after transplantation. In the longer perspective DGF is associated with increased risk of graft failure, thus decreasing the efficacy of the kidney transplantation. Renaparin is a new product under development for the prevention of DGF in association with kidney transplantation. The product binds to the kidney vascular endothelium and its pharmacological effect is based on a local and effective presentation of heparin. Renaparin is administered ex vivo to the kidney by adding it to the preservation solution during Hypothermic Machine Perfusion (HMP) prior to transplantation.

Official Title
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Phase I Double Blind Placebo Controlled Safety Study of ex Vivo Treatment of Kidneys From Deceased Donors With Renaparin®, Followed by Transplantation to Study Population

Conditions
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Delayed Graft Function

Intervention / Treatment
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* Drug: Renaparin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Organs: Kidney must come from a deceased donor above 18 years of age The regular protocols for organ donation according to Swedish law can be followed Patients: Male and female patients 18 - 75 years of age. Ability to provide written informed consent. Mentally stable and able to comply with the procedures of the study protocol Patient has been listed for kidney transplantation from a deceased donor at the clinical sites included in this study. Negative crossmatch test prior to transplantation and no existence of donor-specific antibodies Receiving first or second renal transplantation Exclusion Criteria: Organs: Organs from donors deceased due to cardiac death. Organs which have not been adequately perfused during HMP, as judged by the transplantation surgeon on call. Patients: Use of an investigational drug or other investigational treatment, that could interfere with the outcome of the present trial, in the 30 days' period before Study Day 1 Increased risk of thrombosis (ex. homozygous APC-resistance) or bleeding (INR>1.5) Anticoagulant treatment with Warfarin for indication unrelated to the kidney transplantation History of heparin-induced thrombocytopenia (HIT) History of or positive for HIV, HBV, or HCV History of oncological malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin Scheduled to undergo multi-organ transplantation or dual kidney transplantation Current drug and/or alcohol abuse Known fish allergy History or presence of a medical condition or disease or psychiatric condition that in the investigator's assessment would place the patient at an unacceptable risk for study participation Lactating or pregnant women or women who intend to become pregnant Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during study treatment. Acceptable birth control methods are those with a failure rate of less than 1% per year when used consistently and correctly. Such methods include (in Recommendations related to contraception and pregnancy testing in clinical trials, supplied from www.hma.eu/): Combined (estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation oral intravaginal transdermal progestogen-only hormonal contraception associated with inhibition of ovulation oral injectable implantable intrauterine device intrauterine hormone-releasing system bilateral tubal occlusion vasectomized partner Patients who the investigator considers not eligible to give informed consent Presence of ECG-based evidence of acute myocardial infarction, unstable angina, decompensated heart failure, third degree of heart block or cardiac arrhythmia associated with hemodynamic stability Patients with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo a kidney transplantation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Renaparin<br>Solution administered once to kidney ex-vivo | Drug: Renaparin<br>* 50 mL added at one occasion ex-vivo to machine perfusion solution to treat kidney at least 3 hours prior to transplantation<br>|
| Placebo Comparator: Placebo<br>Placebo administered once to kidney ex-vivo | Drug: Placebo<br>* 50 mL added at one occasion ex-vivo to machine perfusion solution to treat kidney at least 3 hours prior to transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number and severity grade of Serious Adverse Events and Adverse Events including description of their associated MedDRA terms during the first 30 days after transplantation. | 30 days |