A randomised controlled investigation into the efficacy of heme arginate in improving primary graft function in deceased donor kidney transplantation

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). - The HOT 2 Trial

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2018-000131-27-GB

Enrollment

600

Registered

2018-06-13

Start date

2018-05-23

Completion date

Unknown

Last updated

2025-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

End stage renal disease patients undergoing a deceased donor kidney transplant MedDRA version: 20.0 Level: LLT Classification code 10023438 Term: Kidney transplant System Organ Class: 100000004865

Interventions

Trade Name: Normosang Product Name: Normosang Pharmaceutical Form: Concentrate for solution for injection/infusion INN or Proposed INN: Human Hemin Other descriptive name: Normosang Concentration unit

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Patients undergoing a kidney only transplant, or a dual kidney transplant, from a deceased donor will be invited to take part. • All participants will be at least 18 years old. There is no upper age limit. • All patients receiving standard immunosuppression for the individual centre will be included. • Meets the co-enrolment criteria outlined in section 4.4 of the protocol Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50

Exclusion criteria

Exclusion criteria: • Kidney transplant patients as part of a multi-organ transplant e.g. with pancreas or liver • Hepatitis C (HCV) +ve donor to HCV –ve recipient • Known hypersensitivity to heme arginate • Unable to give informed consent • Patients with porphyria, irrespective of whether they have ever 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.

Design outcomes

Primary

Measure	Time frame
Main Objective: Does Heme Arginate (HA) result in transplanted kidneys working quicker (reduction in delayed graft function) after transplantation compared with the placebo group. ;Secondary Objective: Secondary objectives are: •To reduce the requirement for dialysis during the week post transplantation •To reduce the number of days to functioning graft •To determine if treatment influences renal function and acute rejection rates in the first 3 months •To determine whether treatment impacts on early post-transplant quality of life (first 3 months) ;Primary end point(s): Delayed Graft Function (DGF) - defined as a failure of a spontaneous fall in creatinine of >10% for each 3 consecutive day period in the first week following transplantation, or equivalent. ;Timepoint(s) of evaluation of this end point: Daily for the first seven days post transplant or until discharge from hospital if before day 7 post-op.	—

Measure

Time frame

Main Objective: Does Heme Arginate (HA) result in transplanted kidneys working quicker (reduction in delayed graft function) after transplantation compared with the placebo group. ;Secondary Objective: Secondary objectives are: •To reduce the requirement for dialysis during the week post transplantation •To reduce the number of days to functioning graft •To determine if treatment influences renal function and acute rejection rates in the first 3 months •To determine whether treatment impacts on early post-transplant quality of life (first 3 months) ;Primary end point(s): Delayed Graft Function (DGF) - defined as a failure of a spontaneous fall in creatinine of >10% for each 3 consecutive day period in the first week following transplantation, or equivalent. ;Timepoint(s) of evaluation of this end point: Daily for the first seven days post transplant or until discharge from hospital if before day 7 post-op.

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Secondary

Measure	Time frame
Secondary end point(s): i. Requirement for dialysis during the week post transplantation ii. Number of days to functioning graft (defined as a spontaneous fall in creatinine of =10% over a period of 3 consecutive days in the first 7 days post-transplant, or equivalent). iii. Length of stay on index admission for transplant iv. Serum creatinine at 1 and 3 months’ post-transplant v. Biopsy-proven acute rejection during first 3 months vi. SF-36 quality of life questionnaire at days 0 (pre-transplant), 7 and approximately three months post-transplant vii. Cost-effectiveness (Cost per QALY gained) ;Timepoint(s) of evaluation of this end point: i. Daily for the first seven days post transplant or until discharge from hospital if before day 7 post-op. ii. Daily for the first seven days post transplant or until discharge from hospital if before day 7 post-op. iii. Confirmed at day 30 post-op if discharge is not within the first 7 days post transplant. iv. Assessed/confirmed at follow up appointment on day 90 post-op v. Completed at Day 0, 7 and 90 post transplant vi. Assessed as part of trial analysis using data collected throughout the course of the patient participation in the trial.	—

Measure

Time frame

Secondary end point(s): i. Requirement for dialysis during the week post transplantation ii. Number of days to functioning graft (defined as a spontaneous fall in creatinine of =10% over a period of 3 consecutive days in the first 7 days post-transplant, or equivalent). iii. Length of stay on index admission for transplant iv. Serum creatinine at 1 and 3 months’ post-transplant v. Biopsy-proven acute rejection during first 3 months vi. SF-36 quality of life questionnaire at days 0 (pre-transplant), 7 and approximately three months post-transplant vii. Cost-effectiveness (Cost per QALY gained) ;Timepoint(s) of evaluation of this end point: i. Daily for the first seven days post transplant or until discharge from hospital if before day 7 post-op. ii. Daily for the first seven days post transplant or until discharge from hospital if before day 7 post-op. iii. Confirmed at day 30 post-op if discharge is not within the first 7 days post transplant. iv. Assessed/confirmed at follow up appointment on day 90 post-op v. Completed at Day 0, 7 and 90 post transplant vi. Assessed as part of trial analysis using data collected throughout the course of the patient participation in the trial.

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Countries

United Kingdom

Contacts

Public ContactJean Antonelli

Edinburgh Clinical Trials Unit, University of Edinburgh

hot2@ed.ac.uk01316519920

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026