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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified May 2013 by University College, London
Sponsor:
Collaborator:
University College London Hospitals
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01864252
First received: April 29, 2013
Last updated: October 31, 2013
Last verified: May 2013
  Purpose

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).


Condition Intervention Phase
Myocardial Reperfusion Injury
Other: Remote ischaemic preconditioning
Drug: IV Normal saline
Drug: IV Glyceryl trinitrate 2-5ml/h
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Remote Ischaemic Preconditioning and Glyceryl Trinitrate on Peri-operative Myocardial Injury in Cardiac Bypass Surgery Patients (ERIC-GTN Study)

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Troponin T area under the curve [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    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:
  • Inotrope/Vasopressor requirements peri-operatively [ Time Frame: Post-operative day 1,2,3 and 4 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    A record of stay in days will be noted

  • Length of hospital stay [ Time Frame: Average 14 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 260
Study Start Date: December 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01864252

Contacts
Contact: Derek M Yellon, PhD DSC FACC 02034479888 D.Yellon@ucl.ac.uk
Contact: Vivek Sivaraman, MRCP MD FRCA 02034479888 Vivek.Sivaraman@ucl.ac.uk

Locations
United Kingdom
The Heart Hospital, UCL Hospitals NHS Trust Not yet recruiting
London, United Kingdom, NW1 2PG
Contact: Vivek Sivaraman, MRCP MD FRCA    02034479781    Vivek.Sivaraman@ucl.ac.uk   
Principal Investigator: Derek M Yellon, PhD DSc FACC         
Principal Investigator: Derek J Hausenloy, MD PhD FRCP         
Sub-Investigator: Vivek Sivaraman, MRCP MD FRCA         
Sub-Investigator: Shyam Kolvekar, MS MCh FRCS         
Sub-Investigator: Roger Cordery, BSc FRCA         
Sub-Investigator: Maria Xenou, BSc , MSc         
Sponsors and Collaborators
University College, London
University College London Hospitals
Investigators
Principal Investigator: Derek Yellon, PhD DSc FRCP The Hatter Cardiovascular Institute
  More Information

No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01864252     History of Changes
Other Study ID Numbers: 120541
Study First Received: April 29, 2013
Last Updated: October 31, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Myocardial Reperfusion Injury
Reperfusion Injury
Wounds and Injuries
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Myocardial Ischemia
Vascular Diseases
Postoperative Complications
Pathologic Processes
Nitroglycerin
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014