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

Primary Purpose

Myocardial Reperfusion Injury

Status
Completed
Phase
Phase 3
Locations
United Kingdom
Study Type
Interventional
Intervention
Remote ischaemic preconditioning
IV Normal saline
IV Glyceryl trinitrate 2-5ml/h
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myocardial Reperfusion Injury

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Heart Hospital, UCL Hospitals NHS Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Sham Comparator

Active Comparator

Experimental

Experimental

Arm Label

Group 1 Control (65 patients)

Group 2 (65 patients)

Group 3 GTN (65 patients):

• Group 4 RIPC+GTN (65 patients):

Arm Description

Sham Remote ischaemic preconditioning with IV normal saline 2-5ml/hour.

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.

Patients administered sham simulated Remote Ischaemic Preconditioning protocol prior to surgery and IV Glyceryl Trinitrate 2-5ml/h during surgery.

Patients administered Remote Ischaemic Preconditioning protocol and IV Glyceryl Trinitrate during surgery

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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]
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.
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.
Length of ITU stay
A record of stay in days will be noted
Length of hospital stay
Duration of hospital stay will be recorded in days
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

Full Information

First Posted
April 29, 2013
Last Updated
September 24, 2019
Sponsor
University College, London
Collaborators
University College London Hospitals
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1. Study Identification

Unique Protocol Identification Number
NCT01864252
Brief Title
Investigation Into the Role of GTN & RIPC in Cardiac Surgery
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
January 2014 (Actual)
Primary Completion Date
October 2018 (Actual)
Study Completion Date
February 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
Collaborators
University College London Hospitals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Reperfusion Injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
192 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1 Control (65 patients)
Arm Type
Sham Comparator
Arm Description
Sham Remote ischaemic preconditioning with IV normal saline 2-5ml/hour.
Arm Title
Group 2 (65 patients)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Group 3 GTN (65 patients):
Arm Type
Experimental
Arm Description
Patients administered sham simulated Remote Ischaemic Preconditioning protocol prior to surgery and IV Glyceryl Trinitrate 2-5ml/h during surgery.
Arm Title
• Group 4 RIPC+GTN (65 patients):
Arm Type
Experimental
Arm Description
Patients administered Remote Ischaemic Preconditioning protocol and IV Glyceryl Trinitrate during surgery
Intervention Type
Other
Intervention Name(s)
Remote ischaemic preconditioning
Intervention Description
3 cycles of 5 minutes to arm and legs
Intervention Type
Drug
Intervention Name(s)
IV Normal saline
Intervention Description
Normal saline IV started prior to knife to skin at a rate of 2-5 mls/h and stopped just after weaning off bypass.
Intervention Type
Drug
Intervention Name(s)
IV Glyceryl trinitrate 2-5ml/h
Intervention Description
IV GTN given during surgery started prior to knife to skin and stopped after weaning off cardiopulmonary bypass.
Primary Outcome Measure Information:
Title
Troponin T area under the curve
Description
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.
Time Frame
72 hours
Secondary Outcome Measure Information:
Title
Inotrope/Vasopressor requirements peri-operatively
Description
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]
Time Frame
Post-operative day 1,2,3 and 4
Title
Ventilator dependence post operatively
Description
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.
Time Frame
Post-operative day 1,2,3 and 4
Title
Incidence of Acute Kidney Injury assessed using biomarkers
Description
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.
Time Frame
Post-operative day 1,2,3 and 4
Title
Length of ITU stay
Description
A record of stay in days will be noted
Time Frame
Average 4 days
Title
Length of hospital stay
Description
Duration of hospital stay will be recorded in days
Time Frame
Average 14 days
Title
Incidence of post-operative atrial fibrillation
Description
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
Time Frame
Post-operative day 1,2,3 and 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Derek Yellon, PhD DSc FRCP
Organizational Affiliation
The Hatter Cardiovascular Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Heart Hospital, UCL Hospitals NHS Trust
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
26412308
Citation
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.
Results Reference
derived

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Investigation Into the Role of GTN & RIPC in Cardiac Surgery

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