Heme Arginate in Transplantation Study

Renal Transplant Rejection Clinical Trial

— HOT2  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03646344
• Other study ID #: AC17065
• Status: Terminated
• Phase: Phase 3
• Start date: March 12, 2019
• Est. completion date: February 23, 2021

Study information

• Verified date: June 2021
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 47
• Est. completion date: February 23, 2021
• Est. primary completion date: March 17, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Delayed Graft Function
• Renal Transplant Failure
• Renal Transplant Rejection

Intervention

Drug:
• Heme 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).
• 0.9% 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).

Locations

Country	Name	City	State
United Kingdom	Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh	Edinburgh
United Kingdom	NHS Lothian - Royal Infirmary of Edinburgh	Edinburgh	Lothian

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	Kidney Cancer UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	1 year
Other	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.	1 year
Primary	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	Requirement for dialysis	The number of participants requiring dialysis within the first week post-transplant	1 week post transplant
Secondary	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	1 week
Secondary	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)	3 months
Secondary	Creatinine levels	Serum creatinine levels at 1 and 3 months post-transplant across both randomised groups	3 months
Secondary	Acute rejection	The number of participants with biopsy-proven acute rejection within the first 3 months post-transplant	3 months
Secondary	SF36 Quality of Life	A comparison of differences between groups in patient reported quality of life using the SF36	Up to 3 months post transplant
Secondary	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	Up to 3 months post transplant