Clinical trial NCT03646344: Heme Arginate in Transplantation Study
Official title: Heme Arginate in Transplantation Study - a Multi-centre Blinded Parallel-group Randomised Trial of Heme Arginate Versus Placebo to Reduce Delayed Graft Function in Kidney Transplant Recipients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Renal Transplant Rejection
Renal Transplant Failure
Keywords: Deceased donor renal transplantation
Heme Arginate
Delayed graft function
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: Kidney Cancer UK
First posted: 2018-08-24
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-centre, parallel group 1:1 randomised placebo controlled trial
Primary purpose: TREATMENT

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.


Eligibility criteria: 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:

* 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

Primary outcomes:
measure: Delayed Graft Function
timeFrame: 1 week post transplant
Secondary outcomes:
measure: Requirement for dialysis
timeFrame: 1 week post transplant
measure: Time to functioning graft
timeFrame: 1 week
measure: Length of hospital stay
timeFrame: 3 months
measure: Creatinine levels
timeFrame: 3 months
measure: Acute rejection
timeFrame: 3 months
measure: SF36 Quality of Life
timeFrame: Up to 3 months post transplant
measure: Cost per QALY gained
timeFrame: Up to 3 months post transplant
Other outcomes:
measure: 1 Year graft survival
timeFrame: 1 year
measure: 1 year recipient survival
timeFrame: 1 year
Locations:
city: Edinburgh
country: United Kingdom
facility: NHS Lothian - Royal Infirmary of Edinburgh
state: Lothian
city: Edinburgh
country: United Kingdom
facility: Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh
Study officials:
affiliation: University of Edinburgh
name: Lorna Marson
role: PRINCIPAL_INVESTIGATOR
References: