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TerminatedNCT03646344HOT2Updated Nov 17, 2025

Heme Arginate in Transplantation Study

A Phase 3 interventional study of Heme Arginate 25 MG/ML and 0.9% Sodium-chloride in Renal Transplant Rejection and Renal Transplant Failure, sponsored by University of Edinburgh. Terminated at 2 sites in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-11-17.

Sponsored by University of Edinburgh · Phase 3, Interventional, and Treatment

Why this study was terminated
COVID
Phase
Phase 3
Study type
Interventional
Enrollment
47
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Renal Transplant Rejection
  • Renal Transplant Failure

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Keywords

  • Deceased donor renal transplantation
  • Heme Arginate
  • Delayed graft function
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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

Exclusion criteria

Exclusion Criteria:

  • 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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
47 participants (actual)

Study arms

  • Active comparator
    Active Group

    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 comparator
    Placebo Group

    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

  • DrugHeme Arginate 25 MG/ML

    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).

  • Drug0.9% Sodium-chloride

    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).

05

What researchers measure

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.

    Time frame: 1 week post transplant

Secondary outcomes

  1. Requirement for dialysis

    The number of participants requiring dialysis within the first week post-transplant

    Time frame: 1 week post transplant

  2. Time to functioning graft

    The number of days to functioning graft, defined as the spontaneous fall in creatinine of greater than, or equal to 10% over a period of 3 consecutive days in the first 7 days post transplant

    Time frame: 1 week

  3. Length of hospital stay

    The number of days spent in hospital, along with level of care (ward/HDU/ITU), for the index admission (transplantation admission)

    Time frame: 3 months

  4. Creatinine levels

    Serum creatinine levels at 1 and 3 months post-transplant across both randomised groups

    Time frame: 3 months

  5. Acute rejection

    The number of participants with biopsy-proven acute rejection within the first 3 months post-transplant

    Time frame: 3 months

  6. SF36 Quality of Life

    A comparison of differences between groups in patient reported quality of life using the SF36

    Time frame: Up to 3 months post transplant

  7. Cost per QALY gained

    Using data derived from the SF36 to weight survival for quality of life, Quality Adjusted Life Year (QALY) will be assessed

    Time frame: Up to 3 months post transplant

Other outcomes

  1. 1 Year graft survival

    Graft survival rates at 1 year post transplant will be obtained from routinely collected data and differences between treatment groups assessed.

    Time frame: 1 year

  2. 1 year recipient survival

    Recipient survival rates at 1 year post transplant will be obtained from routinely collected data and differences between treatment groups assessed.

    Time frame: 1 year

06

Study locations

2 sites
  • NHS Lothian - Royal Infirmary of Edinburgh
    Edinburgh, Lothian EH16 4SA, United Kingdom
  • Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh
    Edinburgh, EH16 4UX, United Kingdom
07

References and documents

Individual participant data

Plan to share: Yes — Following publication of the primary paper, a de-identified individual participant data set will be submitted to a data archive for sharing purposes. Access to this data set will be under a controlled access model in line with ECTU policies at that time.

Supporting information: Study protocol, Sap

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03646344
Lead sponsor
University of Edinburgh
Collaborators
Kidney Cancer UK
Responsible party
Sponsor
First posted
Aug 24, 2018
Start date
Mar 12, 2019
Primary completion
Mar 17, 2020
Completion
Feb 23, 2021
Last update
Nov 17, 2025

Study contacts

Lorna Marson
principal investigator · University of Edinburgh

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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