Ischemia-reperfusion (IR) InjuryPhase 3NCT00650507
Clinical and Genomic Responses to Open Heart Surgery
A Phase 3 study testing Remote ischemic preconditioning (RIPC) in people with Ischemia-reperfusion (IR) Injury, run by The Hospital for Sick Children at 1 site in Canada.
Trial summary
This study will be the first large scale randomized study of remote ischemic preconditioning (RIPC) ever performed and will define the role of this novel therapy as a clinical tool. Read more about this study
- Who is it for?
- Ages 1 day to 17 years
- Conditions the study is for
- Ischemia-reperfusion (IR) Injury
- What is being tested?
- Remote ischemic preconditioning (RIPC)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2008to Dec 2012
- 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 1 day to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Subject age birth (>36 weeks gestation) to 17 years.
- Underlying cardiac anatomy and planned primary repair with no anticipated residual shunting. Repair must necessitate use of cardiopulmonary bypass.
- Informed consent/assent of subject, parent(s) or legal guardian as appropriate.
Who cannot join
- Current or recent ischemic insult, defined as vascular occlusion or episode of cardiorespiratory collapse requiring medical intervention occurring within 7 days of enrollment.
- Evidence in any system for organ dysfunction that requires medical intervention.
- Current treatment with systemic anticoagulation therapy or the presence of a bleeding diathesis.
- Presence of important pulmonary or airway disease requiring medical intervention.
- Current or previous (within 10 days of screening) use of systemic corticosteroids.
- Recent (within 7 days of screening) or current documented systemic infection or sepsis.
- Anticipated unavailability of an uninstrumented limb with no anatomic or physiologic abnormality precluding administration of RIPC stimulus using a standard blood pressure cuff.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical and Genomic Responses to Open Heart Surgery: A Randomized Controlled Trial of the Effects of Remote Ischemic Preconditioning
This study will be the first large scale randomized study of remote ischemic preconditioning (RIPC) ever performed and will define the role of this novel therapy as a clinical tool. This study will also be the first to define preoperative gene expression profiles associated with poor postoperative outcomes in a control (SHAM) population of children undergoing cardiac surgery. Finally, the role of RIPC in modifying these gene expression profiles will be examined. Therefore, mechanistic insight into the proven ability of RIPC to improve markers of tissue injury, and the expected improvement in clinically relevant endpoints, will be examined.
Read the detailed description
Remote ischemic preconditioning (RIPC) is a powerful, innate mechanism of protection against ischemia-reperfusion (IR) injury. During the course of previous investigations, it was shown in animal models that transient limb ischemia (our stimulus for generating remote ischemic preconditioning) leads to induction of a portfolio of myocardial genomic responses concerned with stress-response and repair mechanisms, reduces myocardial infarction after prolonged coronary occlusion, protects against cardiopulmonary bypass-induced neural, pulmonary and myocardial damage, and when administered to the recipient, reduces IR injury in the transplanted heart.
In humans, it has been have shown that RIPC downregulates genes responsible for pro-inflammatory pathways concerned with TNFα-signaling, apoptosis and exocytosis in circulating leukocytes, reduces ischemia-induced endothelial dysfunction, and decreases markers of myocardial and lung injury in a pilot study of children undergoing open heart surgery. However, the latter study was not powered to demonstrate differences in anatomic and age-related subgroups, or clinically relevant 'hard' end-points such as ventilation time, intensive care, and length of hospital stay.
Thus, we are now proposing a large-scale clinical study examining genetic predictors of clinically relevant postoperative outcomes, and how they are modified by remote preconditioning.
- Conditions
- Ischemia-reperfusion (IR) Injury
- Being tested
- Remote ischemic preconditioning (RIPC), SHAM
- Keywords
- children, cardiac surgery, remote ischemic preconditioning, SHAM, ischemia-reperfusion
- Medical subject headings
- Wounds and Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remote ischemic preconditioning (RIPC)Procedure or surgery
The RIPC stimulus will be delivered in the OR prep room after the induction of anesthesia (while the anesthesiologist and staff are inserting vascular cannulae and preparing the patient for surgery). Whenever possible, the left lower limb will be selected for delivery of the stimulus. An appropriate sized cuff will be selected and connected to a hand aneroid sphygmomanometer. A second cuff and hand aneroid sphygmomanometer will be placed beside the one connected to the study subject. The cuff on the limb will be inflated and deflated to provide a total of four cycles of limb ischemia and reperfusion.
SHAMProcedure or surgery
For this group, the procedure will be identical for that described for the RIPC stimulus, with the exception that the blood pressure cuff placed on the subject will not be inflated, but the second cuff, that has been placed beside, will be inflated.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Procedure: Remote ischemic preconditioning (RIPC) |
| 2 | Active comparator | Not described Receives: Procedure: SHAM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Impact of RIPC on length of hospital stay.
Measured: Assessed through post-operative hospitalization.
Secondary outcomes (5)
Gene expression patterns associated with effects of RIPC.
Measured: Assessed and recorded during the first 24 hours after surgery.
Patterns of baseline gene expression predictive of the clinical and physiologic impact of cardiopulmonary bypass in children (SHAM group only).
Measured: Assessed and recorded during the first 24 hours after surgery.
Impact of RIPC on clinical and physiologic markers related to ischemia-reperfusion injury after cardiac surgery in children.
Measured: Assessed and recorded serially during the first 48 hours after surgery.
Neurodevelopmental Outcomes (Age < 2 years old at surgery)
Patients less than a two years of age at the time of surgery will return at 12 -18 months postoperative to be assessed using the BSID- III. During the same visit, parents will complete questionnaires pertaining to their child's behavior and adaptive behavior; the parent version of the Child Behavior Checklist and the parent version of the Vineland Adaptive Behavior Scales - II.
Measured: Follow-up at 12-18 months post-surgery
Neurodevelopmental Outcomes (Age 2-6 years old at surgery)
Patients greater than two years of age at the time of surgery will be assessed using the Wechsler Preschool and Primary Scale of Intelligence-Revised, the Peabody Picture Vocabulary Test - IV and the Beery-Buktenica Developmental Test of Visual-Motor Integration, 5th Edition. Parents will complete questionnaires pertaining to their child's behavior and adaptive behavior; the parent version of the Child Behavior Checklist and the parent version of the Vineland Adaptive Behavior Scales - II.
Measured: Follow-up at 12-18 months post-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2008 (estimated)
- Study startMar 2008
- Primary completionDec 2012
- Study completionDec 2012
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 Ischemia-reperfusion (IR) InjuryStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian McCrindle, The Hospital for Sick Children
- Investigators
- Brian W. McCrindle, MD MPH, Principal investigator, The Hospital for Sick ChildrenAndrew N. Redington, MB, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00650507
- Sponsor's protocol ID
- 1000011898
- Status last verified
- Aug 2013
- First submitted
- 27 Mar 2008
- Last updated
- 27 Aug 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
McCrindle BW, Clarizia NA, Khaikin S, Holtby HM, Manlhiot C, Schwartz SM, Caldarone CA, Coles JG, Van Arsdell GS, Scherer SW, Redington AN. Remote ischemic preconditioning in children undergoing cardiac surgery with cardiopulmonary bypass: a single-center double-blinded randomized trial. J Am Heart Assoc. 2014 Jul 28;3(4):e000964. doi: 10.1161/JAHA.114.000964.
PubMed 25074698
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Genomic Responses to Open Heart Surgery: A Randomized Controlled Trial of the Effects of Remote Ischemic Preconditioning
- ClinicalTrials.gov ID
- NCT00650507
- Acronym / sponsor ID
- 1000011898
- Conditions
- Ischemia-reperfusion (IR) Injury
- Keywords
- children, cardiac surgery, remote ischemic preconditioning, SHAM, ischemia-reperfusion
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Mar 2008
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 1 Apr 2008 (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 be the first large scale randomized study of remote ischemic preconditioning (RIPC) ever performed and will define the role of this novel therapy as a clinical tool. This study will also be the first to define preoperative gene expression profiles associated with poor postoperative outcomes in a control (SHAM) population of children undergoing cardiac surgery. Finally, the role of RIPC in modifying these gene expression profiles will be examined. Therefore, mechanistic insight into the proven ability of RIPC to improve markers of tissue injury, and the expected improvement in clinically relevant endpoints, will be examined.
Detailed description
Remote ischemic preconditioning (RIPC) is a powerful, innate mechanism of protection against ischemia-reperfusion (IR) injury. During the course of previous investigations, it was shown in animal models that transient limb ischemia (our stimulus for generating remote ischemic preconditioning) leads to induction of a portfolio of myocardial genomic responses concerned with stress-response and repair mechanisms, reduces myocardial infarction after prolonged coronary occlusion, protects against cardiopulmonary bypass-induced neural, pulmonary and myocardial damage, and when administered to the recipient, reduces IR injury in the transplanted heart.
In humans, it has been have shown that RIPC downregulates genes responsible for pro-inflammatory pathways concerned with TNFα-signaling, apoptosis and exocytosis in circulating leukocytes, reduces ischemia-induced endothelial dysfunction, and decreases markers of myocardial and lung injury in a pilot study of children undergoing open heart surgery. However, the latter study was not powered to demonstrate differences in anatomic and age-related subgroups, or clinically relevant 'hard' end-points such as ventilation time, intensive care, and length of hospital stay.
Thus, we are now proposing a large-scale clinical study examining genetic predictors of clinically relevant postoperative outcomes, and how they are modified by remote preconditioning.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Procedure: Remote ischemic preconditioning (RIPC) |
| 2 | Active comparator | Procedure: SHAM |
Who may qualify
- Ages
- 1 day to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Subject age birth (>36 weeks gestation) to 17 years.
- Underlying cardiac anatomy and planned primary repair with no anticipated residual shunting. Repair must necessitate use of cardiopulmonary bypass.
- Informed consent/assent of subject, parent(s) or legal guardian as appropriate.
Key exclusion criteria (7 listed)
- Current or recent ischemic insult, defined as vascular occlusion or episode of cardiorespiratory collapse requiring medical intervention occurring within 7 days of enrollment.
- Evidence in any system for organ dysfunction that requires medical intervention.
- Current treatment with systemic anticoagulation therapy or the presence of a bleeding diathesis.
- Presence of important pulmonary or airway disease requiring medical intervention.
- Current or previous (within 10 days of screening) use of systemic corticosteroids.
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 ischemic preconditioning (RIPC)The RIPC stimulus will be delivered in the OR prep room after the induction of anesthesia (while the anesthesiologist and staff are inserting vascular cannulae and preparing the patient for surgery). Whenever possible, the left lower limb will be selected for delivery of the stimulus. An appropriate sized cuff will be selected and connected to a hand aneroid sphygmomanometer. A second cuff and hand aneroid sphygmomanometer will be placed beside the one connected to the study subject. The cuff on the limb will be inflated and deflated to provide a total of four cycles of limb ischemia and reperfusion. | Procedure or surgery | 1 |
| SHAMFor this group, the procedure will be identical for that described for the RIPC stimulus, with the exception that the blood pressure cuff placed on the subject will not be inflated, but the second cuff, that has been placed beside, will be inflated. | Procedure or surgery | 2 |
Primary outcome
Impact of RIPC on length of hospital stay.
Time frame: Assessed through post-operative hospitalization.
5 secondary outcomes
Gene expression patterns associated with effects of RIPC.
Time frame: Assessed and recorded during the first 24 hours after surgery.
Patterns of baseline gene expression predictive of the clinical and physiologic impact of cardiopulmonary bypass in children (SHAM group only).
Time frame: Assessed and recorded during the first 24 hours after surgery.
Impact of RIPC on clinical and physiologic markers related to ischemia-reperfusion injury after cardiac surgery in children.
Time frame: Assessed and recorded serially during the first 48 hours after surgery.
Neurodevelopmental Outcomes (Age < 2 years old at surgery)
Time frame: Follow-up at 12-18 months post-surgery
Neurodevelopmental Outcomes (Age 2-6 years old at surgery)
Time frame: Follow-up at 12-18 months post-surgery
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 27 Aug 2013.
- Derived from this study: PubMed 25074698McCrindle BW, Clarizia NA, Khaikin S, Holtby HM, Manlhiot C, Schwartz SM, Caldarone CA, Coles JG, Van Arsdell GS, Scherer SW, Redington AN. Remote ischemic preconditioning in children undergoing cardiac surgery with cardiopulmonary bypass: a single-center double-blinded randomized trial. J Am Heart Assoc. 2014 Jul 28;3(4):e000964. doi: 10.1161/JAHA.114.000964.
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.
Brian W. McCrindle, MD MPH principal investigator
The Hospital for Sick Children
Andrew N. Redington, MB principal investigator
The Hospital for Sick Children
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 ischemic preconditioning (RIPC) in people with Ischemia-reperfusion (IR) Injury, run by The Hospital for Sick Children at 1 site in Canada.
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 3 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: finished, as of the sponsor's last update on 27 Aug 2013. 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 Canada. 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. 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?
Impact of RIPC on length of hospital stay. (time frame: Assessed through post-operative hospitalization.). 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 NCT00650507, 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 27 Aug 2013.