Heme Arginate in Transplantation Study

NCT03646344 | Terminated Phase 3 DMC

• 1 other identifier: AC17065
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

Brief Summary

Organ shortage for transplant has necessitated use of kidneys from older donors, increasing the chance that the kidney will not work immediately or for as long as expected. The investigators gave the drug heme arginate (HA) to 20 kidney transplant patients in the first 24 hours after transplant, and showed that it may reduce kidney injury and is safe. The investigators plan to conduct a large study recruiting 600 patients to determine whether HA treatment increases the number of kidney transplants that work immediately. If successful, HA may be introduced into clinical practice at the end of this study. Patients will be invited to take part in the study once listed for a kidney transplant. Further discussions will be had with them when admitted for transplant, and they will be offered the opportunity to participate. Consent will not be taken until the patient is admitted for transplantation. Following consent, participants will be randomised to receive either 2 doses of the study drug, HA, or a salt water solution, one at the time of transplant, and one approximately 24 hours later. Otherwise, treatment will be the same as any other patient undergoing a kidney transplant. Information about recovery from surgery, and specifically about kidney function, will be collected, but will not require additional blood tests. The study period ends after the first 7 days post-transplant, although longer term data will be collected from routine follow up appointments. Participants will be asked to complete a simple quality of life questionnaire 3 times: just before transplant, at approximately one week and three months after transplant.

Conditions

Renal Transplant Rejection; Renal Transplant Failure

Keywords

Deceased donor renal transplantation; Heme Arginate; Delayed graft function

Outcome Measures

Primary Outcomes (1)

• Delayed Graft Function

  The incidence of delayed graft function, defined as failure of a spontaneous fall in creatinine of \>10% for each 3 consecutive day period in the first week following transplantation, with comparison between the two randomised groups.

  1 week post transplant

Secondary Outcomes (7)

• Requirement for dialysis

  1 week post transplant

• Time to functioning graft

  1 week

• Length of hospital stay

  3 months

• Creatinine levels

  3 months

• Acute rejection

  3 months

Other Outcomes (2)

• 1 Year graft survival

  1 year

• 1 year recipient survival

  1 year

Study Arms (2)

Active Group

ACTIVE COMPARATOR

Will receive Heme Arginate (IMP) at a dose of 3mg/kg over 30mins. Participants will receive infusions of the IMP at 2 time-points, the first prior to surgery (transplantation), and the second 20-28 hours later. At each infusion, the IMP will be followed by a 100ml infusion of 0.9% Sodium Chloride over 15mins.

Drug: Heme Arginate 25 MG/ML

Placebo Group

PLACEBO COMPARATOR

Will receive a 100ml infusion of 0.9% Sodium Chloride (placebo) over 30mins. Participants will receive infusions at 2 time-points, the first prior to surgery, and the second 20-28 hours later. At each infusion, the placebo will be followed by a further 100ml infusion of 0.9% Sodium Chloride over 15mins.

Drug: 0.9% Sodium-chloride

Interventions

Heme Arginate 25 MG/ML DRUG

IMP - to be administered at a dose of 3mg/kg to a maximum dose of 250mg over 30 mins. Participants will receive intervention twice during the trial, one on Day 0 (day of transplantation) and then again on D1 (20-28 hours after dose 1).

Active Group

0.9% Sodium-chloride DRUG

Placebo - 100ml of 0.9% Sodium Chloride will be given over 30 mins. Participants will receive intervention twice during the trial, one on Day 0 (day of transplantation) and then again on D1 (20-28 hours after dose 1).

Placebo Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing a kidney only transplant, or a dual kidney transplant, from a deceased donor
• At least 18 years of age, no upper limit
• Receiving standard immunosuppression for the individual centre
• (where applicable) Meets co-enrolment criteria outlined in section 4.4 of the protocol

You may not qualify if:

• Kidney transplant patients as part of a multi-organ transplant e.g. with pancreas or liver
• Known hypersensitivity to heme arginate
• Unable to give informed consent
• Patients with porphyria, irrespective of whether they have received heme arginate or not, will be excluded
• Previous randomisation into this study (or HOT study)
• Women who are pregnant or lactating
• Kidneys that have undergone Ex-vivo Normothermic Perfusion (EVNP)
• Patients with known liver disease, epilepsy, brain injury or disease

Sponsors & Collaborators

• University of Edinburgh: lead
• Kidney Cancer UK: collaborator

Study Sites (2)

NHS Lothian - Royal Infirmary of Edinburgh

Edinburgh, Lothian, EH16 4SA, United Kingdom

Location

Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh

Edinburgh, EH16 4UX, United Kingdom

Location

MeSH Terms

Conditions

Delayed Graft Function

Interventions

heme arginate; Sodium Chloride

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Lorna Marson

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: There will be an unblinded member of the research team (the individual administering the intervention) but otherwise the participant, the other members of the research team, the clinical team and blinded assessors will be blinded to the intervention.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-centre, parallel group 1:1 randomised placebo controlled trial

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: August 24, 2018
• Study Start: March 12, 2019
• Primary Completion: March 17, 2020
• Study Completion: February 23, 2021
• Last Updated: November 17, 2025

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

GB (2)