Investigation Into the Role of GTN & RIPC in Cardiac Surgery

Phase 3

Completed

• Conditions: Myocardial Reperfusion Injury
• Interventions: Drug: IV Glyceryl trinitrate 2-5ml/h; Other: Remote ischaemic preconditioning; Drug: IV Normal saline

• Registration Number: NCT01864252
• Lead Sponsor: University College, London

Brief 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).

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 Timeline

• Study First Submitted: 2013-04-29
• Study First Submitted QC: 2013-05-23
• Study First Posted: 2013-05-29
• Study Start: 2014-01
• Primary Completion: 2018-10
• Study Completion: 2019-02
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-24
• Last Update Posted: 2019-09-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 192

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Group 2 (65 patients)	IV Normal saline	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.
Group 3 GTN (65 patients):	IV Glyceryl trinitrate 2-5ml/h	Patients administered sham simulated Remote Ischaemic Preconditioning protocol prior to surgery and IV Glyceryl Trinitrate 2-5ml/h during surgery.
• Group 4 RIPC+GTN (65 patients):	Remote ischaemic preconditioning	Patients administered Remote Ischaemic Preconditioning protocol and IV Glyceryl Trinitrate during surgery
• Group 4 RIPC+GTN (65 patients):	IV Glyceryl trinitrate 2-5ml/h	Patients administered Remote Ischaemic Preconditioning protocol and IV Glyceryl Trinitrate during surgery
Group 2 (65 patients)	Remote ischaemic preconditioning	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.
Group 1 Control (65 patients)	IV Normal saline	Sham Remote ischaemic preconditioning with IV normal saline 2-5ml/hour.

Primary Outcome Measures

Name	Time	Method
Troponin T area under the curve	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.

Secondary Outcome Measures

Name	Time	Method
Inotrope/Vasopressor requirements peri-operatively	Post-operative day 1,2,3 and 4	The inotrope score will be calculated as follows: Dosages (in μg/kg/min) of \[Dopamine + Dobutamine\] + \[(Adrenaline + Noradrenaline + Isoproterenol + Isoproterenol) x 100\] + \[(Enoximone + Milrinone) x 15\]
Ventilator dependence post operatively	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.
Incidence of Acute Kidney Injury assessed using biomarkers	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.
Length of ITU stay	Average 4 days	A record of stay in days will be noted
Length of hospital stay	Average 14 days	Duration of hospital stay will be recorded in days
Incidence of post-operative atrial fibrillation	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

Trial Locations

Locations (1)

The Heart Hospital, UCL Hospitals NHS Trust; 🇬🇧 London, United Kingdom