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

• ClinicalTrials.gov Identifier: NCT01864252
• Recruitment Status: Completed
• First Posted: May 29, 2013
• Last Update Posted: September 25, 2019
• Sponsor: University College, London
• Collaborator: University College London Hospitals
• Information provided by (Responsible Party): University College, London

Tracking Information

• First Submitted Date: April 29, 2013
• First Posted Date: May 29, 2013
• Last Update Posted Date: September 25, 2019
• Actual Study Start Date: January 2014
• Actual Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 23, 2013)

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.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT01864252 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: May 23, 2013)

• 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]
• 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.
• 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.
• Length of ITU stay [ Time Frame: Average 4 days ]
  A record of stay in days will be noted
• Length of hospital stay [ Time Frame: Average 14 days ]
  Duration of hospital stay will be recorded in 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Investigation Into the Role of GTN & RIPC in Cardiac Surgery
• Official Title: The Effect of Remote Ischaemic Preconditioning and Glyceryl Trinitrate on Peri-operative Myocardial Injury in Cardiac Bypass Surgery Patients (ERIC-GTN Study)
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Care Provider, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Myocardial 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.
• 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.

Study Arms

• Sham Comparator: Group 1 Control (65 patients)
  Sham Remote ischaemic preconditioning with IV normal saline 2-5ml/hour.
  Intervention: Drug: IV Normal saline
• 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.
  Interventions:

  • Other: Remote ischaemic preconditioning
  • Drug: IV Normal saline
• 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.
  Intervention: Drug: IV Glyceryl trinitrate 2-5ml/h
• Experimental: • Group 4 RIPC+GTN (65 patients):
  Patients administered Remote Ischaemic Preconditioning protocol and IV Glyceryl Trinitrate during surgery
  Interventions:

  • Other: Remote ischaemic preconditioning
  • Drug: IV Glyceryl trinitrate 2-5ml/h

• Publications *: Hamarneh A, Sivaraman V, Bulluck H, Shanahan H, Kyle B, Ramlall M, Chung R, Jarvis C, Xenou M, Ariti C, Cordery R, Yellon DM, Hausenloy DJ. The Effect of Remote Ischemic Conditioning and Glyceryl Trinitrate on Perioperative Myocardial Injury in Cardiac Bypass Surgery Patients: Rationale and Design of the ERIC-GTN Study. Clin Cardiol. 2015 Nov;38(11):641-6. doi: 10.1002/clc.22445. Epub 2015 Sep 28.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 24, 2019): 192
• Original Estimated Enrollment (submitted: May 23, 2013): 236
• Actual Study Completion Date: February 2019
• Actual Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01864252
• Other Study ID Numbers: 120541
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University College, London
• Study Sponsor: University College, London
• Collaborators: University College London Hospitals

Investigators

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

• PRS Account: University College, London
• Verification Date: September 2019