The HOT 2 Trial
Research type
Research Study
Full title
Heme arginate in transplantation - a multi-centre blinded parallel-group randomised trial of heme arginate versus placebo to reduce delayed graft function in kidney transplant recipients. (The HOT 2 Trial).
IRAS ID
234635
Contact name
Vikki Young
Contact email
Sponsor organisation
University of Edinburgh
Eudract number
2018-000131-27
Duration of Study in the UK
2 years, 9 months, 30 days
Research summary
Research 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. We 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. We 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 they have been listed for a kidney transplant. Further discussions will be had with them when admitted for a transplant, and they will be offered the opportunity to participate. Consent will not be taken until they are admitted for transplantation. If they agree, they 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, their treatment will be the same as any other patient undergoing a kidney transplant. Information about their recovery from surgery, and specifically about their kidney function, will be collected, but they will not require additional blood tests. The study period ends after the first 7 days after transplant, although longer term data will be collected from routine follow up appointments. Patients will be asked to complete a simple questionnaire about their quality of life 3 times: just before transplant, at approximately one week and three months after transplant.Summary of Results
Background 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 HOT feasibility trial found that kidney transplant patients given the drug heme arginate (HA) in the first 24 hours after transplant may have reduced kidney injury and was safe. The HOT2 trial aimed to assess whether HE resulted in transplanted kidneys working more quickly (reduction in delayed graft function) after transplantation compared with the placebo group where delayed graft function is defined as failure of aspontaneous fall in creatinine of >10% for each 3 consecutive day period in the first week following transplantation, or equivalent.
Methods Phase III multi-centre, parallel group, randomised placebo-controlled trial. Randomisation will be 1:1 between the two treatment arms by minimisation, with minimisation on DBD/DCD (normothermicregional perfusion (NRP))/DCD (cold static storage) and donor age. Participants were allowed to either two doses of HA 25 mg/ml concentrate for solution for infusion at 3mg/kg and diluted in 0.9% sodium chloride (NaCI) or to a saline solution (one at the time transplant, and one approximately 24 hours later). Information about participant recovery from surgery, kidney function and quality of life (as assessed by the SF-36) was collected at 7 days and 90 days post-transplant. Results The HOT2 trial was powered to recruit 600 participants and opened to recruitment on 12 March 2019. The trial recruited 47 (<8% of the total target) at two UK sites when the trial was suspended prematurely on 17 March 2020 as a direct consequence of the COVID-19 pandemic. Data from 37 participants were analysed (HE n=17, placebo n=20). A serious breach involving serial temperature excursions affected 16 participants at a single site (34% of the total recruited). Statistical tests were omitted from the report given the small numbers collected. Conclusions
The HOT2 trial ended prematurely with lessons learnt about the feasibility of complex interventions within kidney transplant trials and the importance of the establishment of a national transplant research network to deliver research and trials in a much more collaborative and focused way.REC name
North East - Newcastle & North Tyneside 2 Research Ethics Committee
REC reference
18/NE/0073
Date of REC Opinion
7 Mar 2018
REC opinion
Favourable Opinion