Renal Transplant RejectionPhase 3HOT2NCT03646344
Heme Arginate in Transplantation Study
A Phase 3 study testing Heme Arginate 25 MG/ML and 0.9% Sodium-chloride in people with Renal Transplant Rejection and Renal Transplant Failure, run by University of Edinburgh at 2 sites in United Kingdom.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Transplant Rejection, Renal Transplant Failure
- What is being tested?
- Heme Arginate 25 MG/ML and 0.9% Sodium-chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 12 Mar 2019to 23 Feb 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
NHS Lothian - Royal Infirmary of Edinburgh
Edinburgh, Lothian, EH16 4SA
Edinburgh Clinical Trials Unit, Usher Institute, University of Edinburgh
Edinburgh, EH16 4UX
About this 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
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.
- Being tested
- Heme Arginate 25 MG/ML, 0.9% Sodium-chloride
- Keywords
- Deceased donor renal transplantation, Heme Arginate, Delayed graft function
- Medical subject headings
- Delayed Graft Function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Heme Arginate 25 MG/MLDrug
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-chlorideDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: 0.9% Sodium-chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 week post transplant
Secondary outcomes (7)
Requirement for dialysis
The number of participants requiring dialysis within the first week post-transplant
Measured: 1 week post transplant
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
Measured: 1 week
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)
Measured: 3 months
Creatinine levels
Serum creatinine levels at 1 and 3 months post-transplant across both randomised groups
Measured: 3 months
Acute rejection
The number of participants with biopsy-proven acute rejection within the first 3 months post-transplant
Measured: 3 months
SF36 Quality of Life
A comparison of differences between groups in patient reported quality of life using the SF36
Measured: Up to 3 months post transplant
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
Measured: Up to 3 months post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2018
- Study start12 Mar 2019
- Primary completion17 Mar 2020
- Study completion23 Feb 2021
Why it stopped: COVID
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Transplant RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multi-centre, parallel group 1:1 randomised placebo controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Kidney Cancer UK
- Responsible party
- Sponsor
- Investigators
- Lorna Marson, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03646344
- Sponsor's protocol ID
- AC17065
- Acronym
- HOT2
- Status last verified
- Jun 2021
- First submitted
- 20 Aug 2018
- Last updated
- 17 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03646344
- Acronym / sponsor ID
- HOT2 / AC17065
- Keywords
- Deceased donor renal transplantation, Heme Arginate, Delayed graft function
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: COVID
- Enrolment
- 47 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- Kidney Cancer UK
- Study start
- 12 Mar 2019 (actual)
- Primary completion
- 17 Mar 2020 (actual)
- Study completion
- 23 Feb 2021 (actual)
- First posted
- 24 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Multi-centre, parallel group 1:1 randomised placebo controlled trial
| Arm | Type | Receives |
|---|---|---|
| Active Group | Active comparator | Drug: Heme Arginate 25 MG/MLWill 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. |
| Placebo Group | Placebo comparator | Drug: 0.9% Sodium-chlorideWill 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Heme Arginate 25 MG/MLIMP - 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). | Drug | Active Group |
| 0.9% Sodium-chloridePlacebo - 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). | Drug | Placebo Group |
Primary outcome
Delayed Graft Function
Time frame: 1 week post transplant
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.
7 secondary outcomes
Requirement for dialysis
Time frame: 1 week post transplant
Time to functioning graft
Time frame: 1 week
Length of hospital stay
Time frame: 3 months
Creatinine levels
Time frame: 3 months
Acute rejection
Time frame: 3 months
SF36 Quality of Life
Time frame: Up to 3 months post transplant
Cost per QALY gained
Time frame: Up to 3 months post transplant
Results and safety
The study was stopped early (reason given: COVID). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2025.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lorna Marson principal investigator
University of Edinburgh
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Heme Arginate 25 MG/ML and 0.9% Sodium-chloride in people with Renal Transplant Rejection and Renal Transplant Failure, run by University of Edinburgh at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: COVID). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Delayed Graft Function (time frame: 1 week post transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2025.