Clinical trial NCT03773211: Renaparin® in Kidney Transplantation
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Delayed Graft Function
Lead sponsor: Corline Biomedical AB
Sponsor class: INDUSTRY
First posted: 2018-12-12
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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/):

  1. Combined (estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation

     * oral
     * intravaginal
     * transdermal
  2. progestogen-only hormonal contraception associated with inhibition of ovulation

     * oral
     * injectable
     * implantable
  3. intrauterine device
  4. intrauterine hormone-releasing system
  5. bilateral tubal occlusion
  6. 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

Primary outcomes:
measure: Adverse Events
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Transplantationscentrum, Sahlgrenska University Hospital
city: Stockholm
country: Sweden
facility: Department of Transplantation Surgery, Karolinska University Hospital, Huddinge
city: Uppsala
country: Sweden
facility: Department of Surgical Sciences, Section of Transplantation Surgery, Uppsala University Hospital
Study officials:
affiliation: Section of Transplantation Surgery, Uppsala University Hospital
name: Amir Sedigh, MD
role: PRINCIPAL_INVESTIGATOR
References: