E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ischaemia-reperfusion injury in renal transplantation |
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E.1.1.1 | Medical condition in easily understood language |
The inevitable kidney damage that happens after transplant due to interruption in blood flow. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Cell Physiological Phenomena [G04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014646 |
E.1.2 | Term | End stage renal disease (ESRD) |
E.1.2 | System Organ Class | 100000004857 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023438 |
E.1.2 | Term | Kidney transplant |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Does treating the recipients of deceased donor kidneys with heme-arginate (HA) increase the amount of HO-1 protein in the recipient’s white blood cells compared to placebo treatment? |
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E.2.2 | Secondary objectives of the trial |
Does treating the recipients of deceased donor kidneys with heme-arginate (HA) increase the amount of HO-1 mRNA in the recipient’s white blood cells compared to placebo treatment at 24 hours?
How does the recipient's white blood cell HO-1 mRNA and protein expression change over the 5 days after HA/placebo injection?
Does treating the recipients of deceased donor kidneys with heme-arginate (HA) increase HO-1 protein expression in the transplanted kidney at day 5 compared to placebo treatment?
Does HA improve outcome after transplantation by preventing delayed graft function compared to placebo?
Does HA treatment reduce histological injury in the transplanted kidney compared to placebo treatment?
Can we predict the amount of injury a transplanted kidney has sustained by measuring biological markers in the urine?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All patients receiving a single kidney deceased donor transplant. All patients receiving standard immunosuppression. |
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E.4 | Principal exclusion criteria |
Patients unable to receive the standard immunosuppressive regimen Patients unable to give informed consent Patients with known hypersensitivity reactions to HA Patients receiving more than one organ Patients receiving their 3rd or subsequent kidney transplant Patients who are fully anticoagulated pre-operatively Patients on combined anti-platelet agents
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is the difference in HO-1 protein expression in the recipient monocyte/macrophages between pre-infusion and 24 hours post-infusion levels as measured by Western Blot comparing Heme-arginate (HA) with placebo.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Blood test at 24 hours after HA infusion. We are allowing an eight hour window (20-28 hours post-infusion)for this blood test. |
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E.5.2 | Secondary end point(s) |
The difference in levels of HO-1 mRNA as measured by PCR in the recipient monocytes/macrophages between the pre-infusion sample and the 24 hours post-infusion samples comparing HA vs. placebo.
The difference in levels of HO-1 expression in the transplanted kidney as determined by immunohistochemical analysis between the pre-operative biopsy sample and the day 5 biopsy sample in participants who have received HA vs. those that have received placebo.
The difference in histological injury in the transplanted kidney as determined by the Pathologist between the pre-operative sample and the day 5 sample comparing HA to placebo.
The difference in incidence of delayed graft function in participants who received HA compared to placebo.
We will determine whether the level of urinary biomarkers in post-transplant urine samples by ELISA has a relationship with with poor renal function in transplant recipients as determined by the incidence of delayed graft function.
The pattern of the change in recipient's white blood cell HO-1 mRNA and protein expression over the 5 days of the study for both HA treatment group and placebo treatment group. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The HO-1 mRNA induction in monocytes is measured at 24 hours post infusion (blood sample window of 20-28 hours).
HO-1 induction in renal tissue and histological renal injury is measured at 5 days post transplant.
Delayed graft function is assessed from the results of daily routine blood tests from day 1 to day 7 post transplant.
Urinary biomarkers will be measured daily from day 1-5 when the participant starts producing urine.
The pattern of the monocyte HO-1 expression will be evaluated from samples taken pre-operatively and on days 1-5 post-op.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is defined as the discharge of the last patient from hospital or day 7 of their in-patient stay, which ever is earlier. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 28 |