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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-004311-23 | EudraCT Number |
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| Name | Class |
|---|---|
| NHS Lothian | OTHER_GOV |
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This is a blinded, placebo-controlled, randomised controlled trial looking at the effects of Heme arginate (HA) on cadaveric renal transplantation. The investigators know that HA can upregulate HO-1, which has been shown to have a protective effect on animal transplants.
The investigators will be giving HA/placebo to participants prior to transplant and repeat again on day 2 post-transplant and compare outcomes.
Patients will be recruited from the East of Scotland transplant waiting list and consent when they arrive in the hospital. The investigators will randomise them to drug or placebo and give the infusion prior to induction for their transplant.
A blood sample will be taken prior to infusion and a renal biopsy will be taken before the graft is implanted. These will be used as baseline values.
Patients will receive standard care from our unit. The investigators will use the routine blood test results (urea and creatinine) to determine the function of the graft.
The investigators will take blood samples 24 hours after infusion of drug/placebo and use this to determine the primary outcome. Blood tests will be taken daily and a renal biopsy taken on day 5 to fulfil secondary objectives.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Heme arginate (Normosang) | Active Comparator | This arm will receive 2 doses of Heme Arginate (trade name Normosang); 1 dose prior to transplant and another on day 2. This is a product derived from human hemin and has been used for over 20 years in clinical practice with few side-effects. |
|
| 0.9% saline | Placebo Comparator | The saline will be given as an IV infusion in the same manner as the Heme Arginate (active comparator) infusion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Heme arginate (Normosang) | Drug | 3mg/kg as a single IV infusion prior to transplant over 30 mins and same dose repeated on day 2 post-transplantation. Each drug infusion will be followed by 100ml saline IV to flush the line. |
| Measure | Description | Time Frame |
|---|---|---|
| Macrophage/monocyte HO-1 protein levels | We will measure the level of HO-1 protein in isolated macrophages/ monocytes in a peripheral blood sample taken at 24 hours after drug infusion | 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Macrophage/monocyte HO-1 mRNA levels | We will measure HO-1 mRNA levels in macrophages/monocytes from a peripheral blood sample taken at 24 hours. | 24 hours |
| HO-1 protein in kidney transplant | We will measure the level of HO-1 protein in kidney tissue from a biopsy sample taken 5 days after drug infusion. This will be compared to baseline |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lorna Marson, MD | Senior Lecturer, Transplant Surgery, University of Edinburgh | Study Director |
| Rachel Thomas, MBChB | Clinical Research Fellow, University of Edinburgh | Principal Investigator |
| Stephen McNally, PhD | University of Edinburgh | Principal Investigator |
| David Kluth, PhD | University of Edinburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Infirmary of Edinburgh/ University of Edinburgh | Edinburgh | Lothian | EH16 4TJ | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26680374 | Derived | Thomas RA, Czopek A, Bellamy CO, McNally SJ, Kluth DC, Marson LP. Hemin Preconditioning Upregulates Heme Oxygenase-1 in Deceased Donor Renal Transplant Recipients: A Randomized, Controlled, Phase IIB Trial. Transplantation. 2016 Jan;100(1):176-83. doi: 10.1097/TP.0000000000000770. |
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| 0.9% sodium chloride | Drug | Solution for infusion, this will be given prior to transplantation and again on day 2; the same as active drug. |
|
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| 5 days |
| Effect on transplanted kidney function | We will record how the kidney functions by determining presence or absence of delayed graft function. | daily for 5 days |
| Urinary biomarkers as markers of injury | We will collect urine to measure the presence of specific urinary biomarkers and correlate with renal function. | daily for 5 days |
| ID | Term |
|---|---|
| D015427 | Reperfusion Injury |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C048849 | heme arginate |
| D006427 | Hemin |
| D012965 | Sodium Chloride |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D006418 | Heme |
| D008665 | Metalloporphyrins |
| D011166 | Porphyrins |
| D045725 | Tetrapyrroles |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010860 | Pigments, Biological |
| D001685 | Biological Factors |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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