Investigation Into the Role of GTN & RIPC in Cardiac Surgery

Myocardial Reperfusion Injury Clinical Trial

— ERIC-GTN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01864252
• Other study ID #: 120541
• Status: Completed
• Phase: Phase 3
• Start date: January 2014
• Est. completion date: February 2019

Study information

• Verified date: September 2019
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: February 2019
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Myocardial Reperfusion Injury
• Reperfusion Injury

Intervention

Other:
• Remote ischaemic preconditioning
3 cycles of 5 minutes to arm and legs

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.
• IV Glyceryl trinitrate 2-5ml/h
IV GTN given during surgery started prior to knife to skin and stopped after weaning off cardiopulmonary bypass.

Locations

Country	Name	City	State
United Kingdom	The Heart Hospital, UCL Hospitals NHS Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	University College London Hospitals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Troponin T area under the curve	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	Inotrope/Vasopressor requirements peri-operatively	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
Secondary	Ventilator dependence post operatively	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
Secondary	Incidence of Acute Kidney Injury assessed using biomarkers	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
Secondary	Length of ITU stay	A record of stay in days will be noted	Average 4 days
Secondary	Length of hospital stay	Duration of hospital stay will be recorded in days	Average 14 days
Secondary	Incidence of post-operative atrial fibrillation	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