Myocardial Reperfusion InjuryPhase 3ERIC-GTNNCT01864252
Investigation Into the Role of GTN & RIPC in Cardiac Surgery
A Phase 3 study testing Remote ischaemic preconditioning, IV Normal saline and IV Glyceryl trinitrate 2-5ml/h in people with Myocardial Reperfusion Injury, run by University College, London at 1 site in United Kingdom.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myocardial Reperfusion Injury
- What is being tested?
- Remote ischaemic preconditioning, IV Normal saline and IV Glyceryl trinitrate 2-5ml/h
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 192 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2014to Feb 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years all patients admitted for on- pump CABG and/or valve surgery
- Able to give consent
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
The Heart Hospital, UCL Hospitals NHS Trust
London, NW1 2PG
About this study
Official title: The Effect of Remote Ischaemic Preconditioning and Glyceryl Trinitrate on Peri-operative Myocardial Injury in Cardiac Bypass Surgery Patients (ERIC-GTN Study)
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).
Read the 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.
- Conditions
- Myocardial Reperfusion Injury
- Being tested
- Remote ischaemic preconditioning, IV Normal saline, IV Glyceryl trinitrate 2-5ml/h
- Medical subject headings
- Myocardial Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote ischaemic preconditioningOther
3 cycles of 5 minutes to arm and legs
IV Normal salineDrug
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/hDrug
IV GTN given during surgery started prior to knife to skin and stopped after weaning off cardiopulmonary bypass.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 Control (65 patients) | Sham comparator | Sham Remote ischaemic preconditioning with IV normal saline 2-5ml/hour. Receives: Drug: IV Normal saline |
| Group 2 (65 patients) | Active comparator | 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. Receives: Other: Remote ischaemic preconditioning; Drug: IV Normal saline |
| Group 3 GTN (65 patients): | Experimental | Patients administered sham simulated Remote Ischaemic Preconditioning protocol prior to surgery and IV Glyceryl Trinitrate 2-5ml/h during surgery. Receives: Drug: IV Glyceryl trinitrate 2-5ml/h |
| • Group 4 RIPC+GTN (65 patients): | Experimental | Patients administered Remote Ischaemic Preconditioning protocol and IV Glyceryl Trinitrate during surgery Receives: Other: Remote ischaemic preconditioning; Drug: IV Glyceryl trinitrate 2-5ml/h |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 72 hours
Secondary outcomes (6)
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]
Measured: Post-operative day 1,2,3 and 4
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.
Measured: Post-operative day 1,2,3 and 4
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.
Measured: Post-operative day 1,2,3 and 4
Length of ITU stay
A record of stay in days will be noted
Measured: Average 4 days
Length of hospital stay
Duration of hospital stay will be recorded in days
Measured: Average 14 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
Measured: Post-operative day 1,2,3 and 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2013 (estimated)
- Study startJan 2014
- Primary completionOct 2018
- Study completionFeb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myocardial Reperfusion InjuryStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- University College London Hospitals
- Responsible party
- Sponsor
- Investigators
- Derek Yellon, PhD DSc FRCP, Principal investigator, The Hatter Cardiovascular Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01864252
- Sponsor's protocol ID
- 120541
- Acronym
- ERIC-GTN
- Status last verified
- Sep 2019
- First submitted
- 29 Apr 2013
- Last updated
- 25 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 26412308
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Remote Ischaemic Preconditioning and Glyceryl Trinitrate on Peri-operative Myocardial Injury in Cardiac Bypass Surgery Patients (ERIC-GTN Study)
- ClinicalTrials.gov ID
- NCT01864252
- Acronym / sponsor ID
- ERIC-GTN / 120541
- Conditions
- Myocardial Reperfusion Injury
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- University College London Hospitals
- Study start
- Jan 2014 (actual)
- Primary completion
- Oct 2018 (actual)
- Study completion
- Feb 2019 (actual)
- First posted
- 29 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1 Control (65 patients) | Sham comparator | Drug: IV Normal salineSham Remote ischaemic preconditioning with IV normal saline 2-5ml/hour. |
| Group 2 (65 patients) | Active comparator | Other: Remote ischaemic preconditioning, Drug: IV Normal salinePatients 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): | Experimental | Drug: IV Glyceryl trinitrate 2-5ml/hPatients 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): | Experimental | Other: Remote ischaemic preconditioning, Drug: IV Glyceryl trinitrate 2-5ml/hPatients administered Remote Ischaemic Preconditioning protocol and IV Glyceryl Trinitrate during surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age > 18 years all patients admitted for on- pump CABG and/or valve surgery
- Able to give consent
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remote ischaemic preconditioning3 cycles of 5 minutes to arm and legs | Other | Group 2 (65 patients), • Group 4 RIPC+GTN (65 patients): |
| IV Normal salineNormal saline IV started prior to knife to skin at a rate of 2-5 mls/h and stopped just after weaning off bypass. | Drug | Group 1 Control (65 patients), Group 2 (65 patients) |
| IV Glyceryl trinitrate 2-5ml/hIV GTN given during surgery started prior to knife to skin and stopped after weaning off cardiopulmonary bypass. | Drug | Group 3 GTN (65 patients):, • Group 4 RIPC+GTN (65 patients): |
Primary outcome
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.
6 secondary outcomes
Inotrope/Vasopressor requirements peri-operatively
Time frame: Post-operative day 1,2,3 and 4
Ventilator dependence post operatively
Time frame: Post-operative day 1,2,3 and 4
Incidence of Acute Kidney Injury assessed using biomarkers
Time frame: Post-operative day 1,2,3 and 4
Length of ITU stay
Time frame: Average 4 days
Length of hospital stay
Time frame: Average 14 days
Incidence of post-operative atrial fibrillation
Time frame: Post-operative day 1,2,3 and 4
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2019.
- Derived from this study: PubMed 26412308Hamarneh 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Derek Yellon, PhD DSc FRCP principal investigator
The Hatter Cardiovascular Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Remote ischaemic preconditioning, IV Normal saline and IV Glyceryl trinitrate 2-5ml/h in people with Myocardial Reperfusion Injury, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Troponin T area under the curve (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01864252, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2019.