Reperfusion InjuryPhase 2/3CREW-INCT02807727
Cardiac REperfusion With Intralipid® at Reperfusion
A Phase 2/3 study testing Intralipid 20% and Modified Ringers Lactate in people with Reperfusion Injury, run by Nkanyiso Hadebe at 1 site in South Africa.
Trial summary
This study will evaluate the benefit of Intralipid® or placebo administered prior to reperfusion to limit ischemia reperfusion injury as measured by the geometric mean difference of the release of troponin I over 72 hours after coronary artery bypass. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Reperfusion Injury
- What is being tested?
- Intralipid 20% and Modified Ringers Lactate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteSouth Africa
- Study dates
- Jan 2017to Jun 2018
- Phase
- Phase 2/3
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- First time elective isolated CABG
- Ejection Fraction greater the 40 by echocardiography or subjectively judged as preserved or good by ventriculography.
- Male and female adults between 18 and 65 years of age.
- Women must have a negative serum pregnancy test at screening.
- Body mass Index (BMI) between 21 and 35 kg/m2.
- Baseline clinical laboratory tests at screening within the reference ranges
Who cannot join
- Received an investigational drug or participated in another research trial within 30 days before the first dose of trial drug or at any time throughout the trial.
- Evidence of current or history of clinically significant oncologic, pulmonary, hepatic with elevated liver functions enzymes 1.5* Upper Limit of Normal (ULN), cardiovascular, haematologic, metabolic, neurological, immunologic, nephrologic, endocrine particularly Diabetes Mellitus as defined by the American Diabetic Association, psychiatric disease, or clinically significant current infection.
- Patients with renal impairment with a creatinine greater than 200 μmol/L
- Evidence of current or history of clinically significant gastrointestinal (excluding appendectomy, cholecystectomy) disease.
- Myocardial infarction within the previous 2 weeks.
- Patients who require inotropic or mechanical cardiac support prior to anaesthesia.
- Contraindication to the trial drugs Previous Hypertriglyceridemia pancreatitis. Hypertriglyceridemia with plasma triglyceride levels > 5.7mmol/L Egg, peanut and soybean allergy.
Trial locations and contacts
1 site in 1 country.
South Africa1 site, 1 recruiting
- Recruiting
Department of Anaesthesia, Groote Schuur Hospital
Cape Town, Western Cape, 7925
Nkanyiso E Hadebe, MBBCh, 0769154990, nkanyiso.hadebe@uct.ac.za
About this study
Official title: Randomised Control Study on Cardiac Protection With Intralipid® in Patients Undergoing Coronary Artery Bypass Grafting on Cardiopulmonary Bypass
This study will evaluate the benefit of Intralipid® or placebo administered prior to reperfusion to limit ischemia reperfusion injury as measured by the geometric mean difference of the release of troponin I over 72 hours after coronary artery bypass.
Read the detailed description
A single center randomised control study on cardiac protection with INTRALIPD in patients undergoing coronary artery bypass grafting on cardiopulmonary bypass.
Purpose and objectives:
Reperfusion after coronary artery bypass grafting is associated with a modifiable leak in cardiac Troponin I (cTnI) secondary to ischemia reperfusion injury. The purpose of the study is to test whether INTRALIPID administered at reperfusion can limit myocardial reperfusion injury as measured by cTnI release in patients undergoing coronary artery bypass grafting.
Trial design:
This study is a prospective single centre double blind placebo controlled randomised trial.
Sample size: 30 Adult Male and Female Patients
Investigational drug(s):
INTRALIPID 20% Fresenius Kabi (SA) Registration Number: K/25.2/316 Formulation: IV Solution Strength: 20% (200mg/ml) Modified Ringer's Lactate Fresenius Kabi (SA) Registration Number: C/24/218 Formulation: IV Solution Dose for both drugs: 1.5 ml/kg Administration: IV Bolus through CVP Blood sampling and tissue biopsies: cTnI will be sampled at fixed time points, baseline 1, 6, 9, 12, 24, 48, and 72 hours after surgery. The first biopsy will be done prior to cardioplegic arrest and the second biopsy will be done 5 minutes after reperfusion.
Safety assessments:
The safety of the interventions will be monitored routinely for all patients and these will focus on:
- Changes in the lipid profile after Intralipid
- Coagulation as measured by ACT, TEG and PFA
- Oxygenation with Arterial Blood Gas monitoring
- Hemodynamic monitoring and echocardiography
- Lipid interference with laboratory measurements. The laboratory will be informed on specimen preparation to avoid interference with instruments
- Post operative hemodynamic Intensive Care Unit Monitoring Measurement will be reported on all safety monitoring and will be considered adverse events where the measured parameter results are out of range from the laboratory references.
Efficacy assessments. Primary endpoint: The efficacy of the drug will be determined by the geometric mean (95% CI) difference in the AUC of the cTnI concentration calculated according to the trapezoid rule.
Secondary End Point: Exploring the molecular mechanism involved in cardiac protection by analyzing tissue sample differences in the phosphorylation cytoplasmic protein kinase.
- Conditions
- Reperfusion Injury
- Being tested
- Intralipid 20%, Modified Ringers Lactate
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intralipid 20%Drug
Also called Lipid Emulsion 20%
Single intravenous bolus dose of 1.5 ml/kg over 3 minutes
Modified Ringers LactateDrug
Also called MRL
Single intravenous bolus dose of 1.5 ml/kg over 3 minutes
| Study group | Role | What they receive |
|---|---|---|
| Intralipid 20% | Active comparator | Intravenous single bolus of 1.5 ml/kg of Intralipid 20% over 3 minutes. Receives: Drug: Intralipid 20% |
| Modified Ringers Lactate | Placebo comparator | Intravenous single bolus of 1.5 ml/kg of MRL over 3 minutes. Receives: Drug: Modified Ringers Lactate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of the serum Troponin I Leak over 72 hours
The primary endpoint will be assessed by the geometric mean (95% CI) difference between the protocol and control groups of the area under the curve for the cTnI concentration in serum over 72 hours (sampled at 1, 6, 12, 24, 48 and 72 hours) calculated according to the trapezoid rule.
Measured: Over 72 hours
Secondary outcomes (1)
Signaling Pathways of intralipid induced cardiac protection
Two right atrial and two left ventricular biopsies will be collected before cardioplegia and the second will be collected 5 minutes prior to reperfusion. These will be used to compare the activation of signalling protein between the groups.
Measured: 5 minutes after reperfusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2016 (estimated)
- Study startJan 2017
- Primary completionJun 2018 (estimated)
- Study completionJun 2018 (estimated)
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 Reperfusion InjuryStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nkanyiso Hadebe
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nkanyiso Hadebe, University of Cape Town
- Investigators
- Nkanyiso E Hadebe, MBBCh, Study chair, University of Cape
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02807727
- Sponsor's protocol ID
- CREW-I
- Acronym
- CREW-I
- Status last verified
- Dec 2017
- First submitted
- 13 Jun 2016
- Last updated
- 12 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: The individual participant data will not be shared
Publications
Hadebe N, Cour M, Imamdin A, Petersen T, Pennel T, Scherman J, Snowball J, Ntsekhe M, Zilla P, Swanevelder J, Lecour S. Cardioprotection with Intralipid During Coronary Artery Bypass Grafting Surgery on Cardiopulmonary Bypass: A Randomized Clinical Trial. Cardiovasc Drugs Ther. 2025 Oct;39(5):1045-1052. doi: 10.1007/s10557-024-07594-w. Epub 2024 Jun 12.
PubMed 38864969
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Control Study on Cardiac Protection With Intralipid® in Patients Undergoing Coronary Artery Bypass Grafting on Cardiopulmonary Bypass
- ClinicalTrials.gov ID
- NCT02807727
- Acronym / sponsor ID
- CREW-I / CREW-I
- Conditions
- Reperfusion Injury
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Nkanyiso HadebeUniversity, hospital or other
- Study start
- Jan 2017
- Primary completion
- Jun 2018 (estimated)
- Study completion
- Jun 2018 (estimated)
- First posted
- 21 Jun 2016 (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.
This study will evaluate the benefit of Intralipid® or placebo administered prior to reperfusion to limit ischemia reperfusion injury as measured by the geometric mean difference of the release of troponin I over 72 hours after coronary artery bypass.
Detailed description
A single center randomised control study on cardiac protection with INTRALIPD in patients undergoing coronary artery bypass grafting on cardiopulmonary bypass.
Purpose and objectives:
Reperfusion after coronary artery bypass grafting is associated with a modifiable leak in cardiac Troponin I (cTnI) secondary to ischemia reperfusion injury. The purpose of the study is to test whether INTRALIPID administered at reperfusion can limit myocardial reperfusion injury as measured by cTnI release in patients undergoing coronary artery bypass grafting.
Trial design:
This study is a prospective single centre double blind placebo controlled randomised trial.
Sample size: 30 Adult Male and Female Patients
Investigational drug(s):
INTRALIPID 20% Fresenius Kabi (SA) Registration Number: K/25.2/316 Formulation: IV Solution Strength: 20% (200mg/ml) Modified Ringer's Lactate Fresenius Kabi (SA) Registration Number: C/24/218 Formulation: IV Solution Dose for both drugs: 1.5 ml/kg Administration: IV Bolus through CVP Blood sampling and tissue biopsies: cTnI will be sampled at fixed time points, baseline 1, 6, 9, 12, 24, 48, and 72 hours after surgery. The first biopsy will be done prior to cardioplegic arrest and the second biopsy will be done 5 minutes after reperfusion.
Safety assessments:
The safety of the interventions will be monitored routinely for all patients and these will focus on:
- Changes in the lipid profile after Intralipid
- Coagulation as measured by ACT, TEG and PFA
- Oxygenation with Arterial Blood Gas monitoring
- Hemodynamic monitoring and echocardiography
- Lipid interference with laboratory measurements. The laboratory will be informed on specimen preparation to avoid interference with instruments
- Post operative hemodynamic Intensive Care Unit Monitoring Measurement will be reported on all safety monitoring and will be considered adverse events where the measured parameter results are out of range from the laboratory references.
Efficacy assessments. Primary endpoint: The efficacy of the drug will be determined by the geometric mean (95% CI) difference in the AUC of the cTnI concentration calculated according to the trapezoid rule.
Secondary End Point: Exploring the molecular mechanism involved in cardiac protection by analyzing tissue sample differences in the phosphorylation cytoplasmic protein kinase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intralipid 20% | Active comparator | Drug: Intralipid 20%Intravenous single bolus of 1.5 ml/kg of Intralipid 20% over 3 minutes. |
| Modified Ringers Lactate | Placebo comparator | Drug: Modified Ringers LactateIntravenous single bolus of 1.5 ml/kg of MRL over 3 minutes. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- First time elective isolated CABG
- Ejection Fraction greater the 40 by echocardiography or subjectively judged as preserved or good by ventriculography.
- Male and female adults between 18 and 65 years of age.
- Women must have a negative serum pregnancy test at screening.
- Body mass Index (BMI) between 21 and 35 kg/m2.
Key exclusion criteria (7 listed)
- Received an investigational drug or participated in another research trial within 30 days before the first dose of trial drug or at any time throughout the trial.
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 |
|---|---|---|
| Intralipid 20%Also: Lipid Emulsion 20%Single intravenous bolus dose of 1.5 ml/kg over 3 minutes | Drug | Intralipid 20% |
| Modified Ringers LactateAlso: MRLSingle intravenous bolus dose of 1.5 ml/kg over 3 minutes | Drug | Modified Ringers Lactate |
Primary outcome
Comparison of the serum Troponin I Leak over 72 hours
Time frame: Over 72 hours
The primary endpoint will be assessed by the geometric mean (95% CI) difference between the protocol and control groups of the area under the curve for the cTnI concentration in serum over 72 hours (sampled at 1, 6, 12, 24, 48 and 72 hours) calculated according to the trapezoid rule.
1 secondary outcome
Signaling Pathways of intralipid induced cardiac protection
Time frame: 5 minutes after reperfusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2017.
- Derived from this study: PubMed 38864969Hadebe N, Cour M, Imamdin A, Petersen T, Pennel T, Scherman J, Snowball J, Ntsekhe M, Zilla P, Swanevelder J, Lecour S. Cardioprotection with Intralipid During Coronary Artery Bypass Grafting Surgery on Cardiopulmonary Bypass: A Randomized Clinical Trial. Cardiovasc Drugs Ther. 2025 Oct;39(5):1045-1052. doi: 10.1007/s10557-024-07594-w. Epub 2024 Jun 12.
- Individual participant dataSharing planned: No. The individual participant data will not be shared
Related trials for Reperfusion Injury
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The Danish Out-of-Hospital Cardiac Arrest Study
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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.
Nkanyiso E Hadebe, MBBCh study chair
University of Cape
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Intralipid 20% and Modified Ringers Lactate in people with Reperfusion Injury, run by Nkanyiso Hadebe at 1 site in South Africa.
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 6 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 12 Dec 2017. 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 South Africa. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nkanyiso E Hadebe, MBBCh (0769154990, nkanyiso.hadebe@uct.ac.za), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of the serum Troponin I Leak over 72 hours (time frame: Over 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 NCT02807727, 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 12 Dec 2017.