Heme Arginate in Cardiac Surgery Patients

NCT02142699 | Completed Phase 2

• 2 other identifiers: SE010472014-001021-32
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

A recent analysis of over 4500 cardiac surgical patients at the Royal Infirmary of Edinburgh has confirmed that acute kidney injury (AKI) is not only a relatively common post-operative complication but is associated with prolonged hospital stay, and increased risk of death. There is currently no specific therapy available except supportive care. In laboratory studies, heme arginate (HA), a drug licensed for human use, has been shown to upregulate the anti-inflammatory enzyme hemeoxygenase-1 (HO-1) and protect aged mice from acute kidney injury. This study will bring this research into the human arena. It will aim to evaluate the minimum effective dose of HA and verify its safety in this specific group of patients. This will be the next step in investigating if HA could be a potential protective treatment for reducing AKI in patients about to have cardiac surgery. Patients who are due to have cardiac surgery and are aged 60 or above will be approached for inclusion in the study. If agreeable, they will be randomly assigned to receive either HA at a dose of 1mg/kg or 3mg/kg. There will be 10 patients in each group. Blood tests will be taken just before the study drug is given, at 6 hours, 24 hours and 7 days post dose. These samples will be used to examine the effect of HA on HO-1 at different doses, and will verify drug safety. Any adverse effects of the drug will be evaluated, although HA has an excellent safety profile when used as it is currently licensed for acute porphyria. Urine samples will also be collected to assess inflammation and quantify urinary biomarkers of AKI. This will set the scene for a randomised clinical trial of HA in cardiac surgical patients at high risk of AKI.

Conditions

Acute Kidney Injury

Keywords

Acute kidney injury; Cardiac surgery; Ischaemia reperfusion injury; hemearginate

Outcome Measures

Primary Outcomes (1)

• Upregulation of Heme oxygenase-1 protein expression in circulating monocytes

  within 3 months of study completion

Secondary Outcomes (4)

• Upregulation of heme oxygenase-1 messenger ribonucleic acid (mRNA) in circulating monocytes

  within 3 months of completion

• Urinary biomarkers of acute kidney injury

  within 3 months of completion of study

• Safety

  at final study visit ie 7 days post dose (or at the resolution of any ongoing adverse event if this lasts longer than 7 days)

• Heme oxygenase-1 (HO-1) Genotype

  within 3 months of study completion

Study Arms (2)

Heme arginate 1mg/kg

ACTIVE COMPARATOR

This is the lower of the 2 doses of Heme arginate (HA). This will be given as a single dose of 1mg/kg on the first study visit. This is given over 1 hour intravenously.

Drug: Heme arginate

Heme arginate 3mg/kg

ACTIVE COMPARATOR

This is the larger dose, Heme arginate 3mg/kg (up to a maximum dose of 250mg) This will be given intravenously, as a single dose on the first study visit, over one hour.

Drug: Heme arginate

Interventions

Heme arginate DRUG

Also known as: Normosang (Orphan Europe)

Heme arginate 1mg/kg; Heme arginate 3mg/kg

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥60
• Planned for elective cardiac surgical procedure:
• Aortic valve replacement
• CABG

You may not qualify if:

• Inability to give informed consent Hypersensitivity to HA Enrolment in other clinical trials Renal replacement therapy Planned for elective cardiac surgical procedure other than CABG or AVR (including combined CABG and AVR) Less than 2 weeks until planned cardiac surgery at time of study drug administration Active infection

Sponsors & Collaborators

• University of Edinburgh: lead
• Medical Research Council: collaborator
• NHS Lothian: collaborator

Study Sites (1)

Royal Infirmary of Edinburgh

Edinburgh, Midlothian, EH16 4SA, United Kingdom

Location

MeSH Terms

Conditions

Acute Kidney Injury; Reperfusion Injury

Interventions

heme arginate

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jeremy Hughes, MD

  Professor of Experimental Nephrology, University of Edinburgh

  PRINCIPAL INVESTIGATOR

• David C Kluth, MD

  Reader in Nephrology, University of Edinburgh

  PRINCIPAL INVESTIGATOR

• Vipin Zamvar, MD

  Royal Infirmary of Edinburgh, NHS Lothian

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2014
• First Posted: May 20, 2014
• Study Start: October 17, 2014
• Primary Completion: October 16, 2015
• Study Completion: November 16, 2015
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

GB (1)