Investigation Into the Role of GTN & RIPC in Cardiac Surgery (ERIC-GTN)

September 24, 2019 updated by: University College, London

The Effect of Remote Ischaemic Preconditioning and Glyceryl Trinitrate on Peri-operative Myocardial Injury in Cardiac Bypass Surgery Patients (ERIC-GTN Study)

The purpose of this study is to determine whether Glyceryl Trinitrate (GTN) reduces injury to the heart during heart-lung bypass surgery in combination with the newer technique of remote ischaemic preconditioning (RIPC).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Ischaemic heart disease is a leading cause of mortality in the western world. A number of patients undergo coronary artery bypass graft (CABG) surgery as treatment for ischaemic heart disease. With the rise of interventional procedures, patients who are coming to have CABG surgery are higher risk1. Remote ischaemic preconditioning (RIPC) has been shown to reduce perioperative myocardial injury (PMI) in patients having CABG even when cold blood cardioplegia or intermittent cross clamp fibrillation is used as cardioprotective measures. These patients have a general anaesthetic with multiple infusions including Glyceryl Trinitrate (GTN). The use of GTN in these patients is based on theoretical assumptions of coronary vasodilation pre operatively along with maintaining graft potency postoperatively. We intend to investigate the effect of GTN in patients undergoing cardiac surgery being subjected to RIPC in its role as a Nitric Oxide (NO) donor. Exogenous NO has been shown to be cardioprotective in animal models.

Study Type

Interventional

Enrollment (Actual)

192

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, NW1 2PG
        • The Heart Hospital, UCL Hospitals NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age > 18 years all patients admitted for on- pump CABG and/or valve surgery
  • Able to give consent

Exclusion Criteria:

  • Allergies to excipients of IMP and placebo
  • Chronic Renal failure (eGFR<30 ml/min/kg)
  • Severe liver disease
  • Peripheral arterial disease
  • Pregnant or lactating women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Sham Comparator: Group 1 Control (65 patients)
Sham Remote ischaemic preconditioning with IV normal saline 2-5ml/hour.
Drug: IV Normal saline
Normal saline IV started prior to knife to skin at a rate of 2-5 mls/h and stopped just after weaning off bypass.
Active Comparator: Group 2 (65 patients)
Patients administered a Remote Ischaemic preconditioning protocol (three-5 min cycles of simultaneous inflation to cuffs placed on upper arm and thigh) prior to surgery and IV normal saline 2-5 mL/h during surgery.
Drug: IV Normal saline
Normal saline IV started prior to knife to skin at a rate of 2-5 mls/h and stopped just after weaning off bypass.
Other: Remote ischaemic preconditioning
3 cycles of 5 minutes to arm and legs
Experimental: Group 3 GTN (65 patients):
Patients administered sham simulated Remote Ischaemic Preconditioning protocol prior to surgery and IV Glyceryl Trinitrate 2-5ml/h during surgery.
Drug: IV Glyceryl trinitrate 2-5ml/h
IV GTN given during surgery started prior to knife to skin and stopped after weaning off cardiopulmonary bypass.
Experimental: • Group 4 RIPC+GTN (65 patients):
Patients administered Remote Ischaemic Preconditioning protocol and IV Glyceryl Trinitrate during surgery
Other: Remote ischaemic preconditioning
3 cycles of 5 minutes to arm and legs
Drug: IV Glyceryl trinitrate 2-5ml/h
IV GTN given during surgery started prior to knife to skin and stopped after weaning off cardiopulmonary bypass.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Troponin T area under the curve
Time Frame: 72 hours
Troponin T area under the curve will be calculated using blood samples collected at 0,6,12,24,48 and 72 hours plotting it against time to calculated AUC.
72 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inotrope/Vasopressor requirements peri-operatively
Time Frame: Post-operative day 1,2,3 and 4

The inotrope score will be calculated as follows:

Dosages (in μg/kg/min) of [Dopamine + Dobutamine] + [(Adrenaline + Noradrenaline + Isoproterenol + Isoproterenol) x 100] + [(Enoximone + Milrinone) x 15]
Post-operative day 1,2,3 and 4
Ventilator dependence post operatively
Time Frame: Post-operative day 1,2,3 and 4
The duration of endotracheal intubation will be noted in hours. Re-intubation rates will be calculated by noting down the number of patients requiring re-intubation and comparing this amongst the 4 groups.
Post-operative day 1,2,3 and 4
Incidence of Acute Kidney Injury assessed using biomarkers
Time Frame: Post-operative day 1,2,3 and 4
Serum creatinine levels will be noted in the first 3 days postoperatively. If a patient requires renal replacement therapy, this will be recorded and comparisons made amongst the groups. Hourly urine output and daily urine volumes for the duration of ITU stay will be recorded.
Post-operative day 1,2,3 and 4
Length of ITU stay
Time Frame: Average 4 days
A record of stay in days will be noted
Average 4 days
Length of hospital stay
Time Frame: Average 14 days
Duration of hospital stay will be recorded in days
Average 14 days
Incidence of post-operative atrial fibrillation
Time Frame: Post-operative day 1,2,3 and 4
Atrial fibrillation will be diagnosed using ECG. A record of the number of patients developing AF post operatively, the intervention used to treat it and whether or not the patient reverted to sinus rhythm prior to ITU discharge will be documented
Post-operative day 1,2,3 and 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Collaborators

University College London Hospitals

Investigators

  • Principal Investigator: Derek Yellon, PhD DSc FRCP, The Hatter Cardiovascular Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2014

Primary Completion (Actual)

October 1, 2018

Study Completion (Actual)

February 1, 2019

Study Registration Dates

First Submitted

April 29, 2013

First Submitted That Met QC Criteria

May 23, 2013

First Posted (Estimate)

May 29, 2013

Study Record Updates

Last Update Posted (Actual)

September 25, 2019

Last Update Submitted That Met QC Criteria

September 24, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 120541

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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