Complication of AnesthesiaPhase 4NCT02299063
Dexmedetomidine Effect on Mitochondrial Function
A Phase 4 study testing Dexmedetomidine and 0.9% NaCl in people with Complication of Anesthesia and Ischaemia-reperfusion Injury, run by The Hospital for Sick Children at 1 site in Canada.
Trial summary
The investigators hypothesize that in addition to a known sympatholytic effect, intraoperative dexmedetomidine reduces adverse changes in mitochondrial function and structure attenuating ischaemia-reperfusion and end-organ injury for children with non cyanotic congenital heart defects having corrective heart surgery. Read more about this study
- Who is it for?
- Ages 3 to 36 months
- Conditions the study is for
- Complication of Anesthesia, Ischaemia-reperfusion Injury
- What is being tested?
- Dexmedetomidine and 0.9% NaCl
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2014to Dec 2019
- Phase
- Phase 4
- 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 3 to 36 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- aged between 3 - 36 months
- having primary corrective heart surgery
Who cannot join
- recent surgery (< 3 months)
- previous chemotherapy
- previous transfusion of blood products
- neurodevelopmental disorders (including Trisomy 21)
- supplemental oxygen requirement (< 3 months)
- asthma requiring regular therapy
Show all 9Show fewer
- obstructive sleep apnea
- the presence of concurrent infection or inflammation
- a known allergy to dexmedetomidine hydrochloride
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Hospital for Sick Children
Toronto, Ontario, M5G1X8
James D O'Leary, MBBCh
John Coles, MD
About this study
Official title: The Protective Effect of the α2-agonist Dexmedetomidine on Mitochondrial Structure and Function for Children With Non-cyanotic Congenital Heart Defects Having Cardiac Surgery: A Randomized Controlled Trial.
The investigators hypothesize that in addition to a known sympatholytic effect, intraoperative dexmedetomidine reduces adverse changes in mitochondrial function and structure attenuating ischaemia-reperfusion and end-organ injury for children with non cyanotic congenital heart defects having corrective heart surgery.
Read the detailed description
PICO: For children with non cyanotic congenital heart defects having corrective heart surgery (P) does intraoperative dexmedetomidine (I) reduce real-time changes in mitochondrial function and content (O) compared with children not receiving dexmedetomidine (C).
The study drug (dexmedetomidine or placebo) will be mixed in a standardized syringe of 4mcg/mL for active syringes or 50mL 0.9% sodium chloride for placebo. Blinded syringes will be prepared by the Research Support Pharmacy.
Administration is via the existing central venous line. A bolus dose of 0.125mL/kg (0.5 mcg/kg dexmedetomidine) infused over 10 minutes will be administered, followed by a continuous infusion for the duration of the surgery. The dexmedetomidine/placebo continuous infusion (CI) dose will run at 0.15mL/kg/hr (0.6 mcg/kg/hr dexmedetomidine).
Blood samples will be obtained from each child at three points in the operating room: 1) after the induction of anesthesia, 2) at the first separation from CPB (prior to administration of blood products), and 3) at the end of the surgery.
Samples obtained will be analyzed for mitochondrial function and morphology, total cellular mitochondrial biomass, and mitochondrial deoxyribonucleic acid (mtDNA) damage:
- After isolating lymphocytes, we will use high content imaging (HCI) to assess mitochondrial function and morphology. The lymphocytes will be stained with tetramethylrhodamine methyl ester (TMRM), which stains mitochondria in proportion to mitochondrial membrane potential, giving a metric for mitochondrial function. In addition, the cells will be stained with MitoTracker Green®, which can be used to assess mitochondrial morphology. Mitochondrial morphology will be quantified in a non-biased fashion using a mathematical image analysis algorithm.
- After extraction of genomic DNA, total cellular mitochondrial biomass and mitochondrial DNA damage will be measured using traditional and long-patch quantitative polymerase chain reaction (PCR).
Myocardial tissue will be also collected prior to closure of the atriotomy. Samples will be placed into 3% buffered glutaraldehyde at the time of biopsy, and imaging of mitochondrial structure using electron microscopy will be performed.
- Being tested
- Dexmedetomidine, 0.9% NaCl
- Keywords
- Mitochondria, Dexmedetomidine, Heart Defects, Congenital
- Medical subject headings
- Reperfusion Injury, Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Precedex
A bolus dose of 0.5 mcg/kg infused over 10 minutes will be administered, followed by a continuous infusion for the duration of the surgery at 0.6 mcg/kg/hr.
0.9% NaClDrug
Also called Normal Saline
| Study group | Role | What they receive |
|---|---|---|
| Placebo (0.9% Saline) | Placebo comparator | 0.9% Saline: bolus dose of 0.125mL/kg infused over 10 minutes, followed by a continuous infusion (CI) dose at 0.15mL/kg/hr for the duration of surgery. Receives: Drug: 0.9% NaCl |
| Dexmedetomidine | Experimental | Dexmedetomidine: bolus dose of 0.5 mcg/kg infused over 10 minutes, followed by a continuous infusion (CI) dose at 0.6 mcg/kg/hr for the duration of surgery. Receives: Drug: Dexmedetomidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mitochondrial function (use high content imaging (HCI)
The primary outcomes for mitochondria will be grouped into mitochondrial function, morphology, content and mtDNA damage.
Measured: Intraoperative
Secondary outcomes (3)
Creatinine level (Marker of acute renal injury)
Marker of acute renal injury
Measured: Postoperative day 1
Cardiac function (Left ventricular ejection fraction measured by trans-thoracic echocardiography)
Left ventricular ejection fraction measured by trans-thoracic echocardiography
Measured: Postoperative day 1
Inotropes and vasopressors (Duration and dose of inotropes and vasopressors after surgery)
Duration and dose of inotropes and vasopressors after surgery
Measured: Postoperative day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2014 (estimated)
- Study startNov 2014
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Complication of AnesthesiaStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James O'Leary, The Hospital for Sick Children
- Investigators
- James D O'Leary, MBBCh, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02299063
- Sponsor's protocol ID
- 1000044746
- Status last verified
- May 2018
- First submitted
- 18 Nov 2014
- Last updated
- 9 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Protective Effect of the α2-agonist Dexmedetomidine on Mitochondrial Structure and Function for Children With Non-cyanotic Congenital Heart Defects Having Cardiac Surgery: A Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT02299063
- Acronym / sponsor ID
- 1000044746
- Keywords
- Mitochondria, Dexmedetomidine, Heart Defects, Congenital
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Nov 2014
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 24 Nov 2014 (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 investigators hypothesize that in addition to a known sympatholytic effect, intraoperative dexmedetomidine reduces adverse changes in mitochondrial function and structure attenuating ischaemia-reperfusion and end-organ injury for children with non cyanotic congenital heart defects having corrective heart surgery.
Detailed description
PICO: For children with non cyanotic congenital heart defects having corrective heart surgery (P) does intraoperative dexmedetomidine (I) reduce real-time changes in mitochondrial function and content (O) compared with children not receiving dexmedetomidine (C).
The study drug (dexmedetomidine or placebo) will be mixed in a standardized syringe of 4mcg/mL for active syringes or 50mL 0.9% sodium chloride for placebo. Blinded syringes will be prepared by the Research Support Pharmacy.
Administration is via the existing central venous line. A bolus dose of 0.125mL/kg (0.5 mcg/kg dexmedetomidine) infused over 10 minutes will be administered, followed by a continuous infusion for the duration of the surgery. The dexmedetomidine/placebo continuous infusion (CI) dose will run at 0.15mL/kg/hr (0.6 mcg/kg/hr dexmedetomidine).
Blood samples will be obtained from each child at three points in the operating room: 1) after the induction of anesthesia, 2) at the first separation from CPB (prior to administration of blood products), and 3) at the end of the surgery.
Samples obtained will be analyzed for mitochondrial function and morphology, total cellular mitochondrial biomass, and mitochondrial deoxyribonucleic acid (mtDNA) damage:
- After isolating lymphocytes, we will use high content imaging (HCI) to assess mitochondrial function and morphology. The lymphocytes will be stained with tetramethylrhodamine methyl ester (TMRM), which stains mitochondria in proportion to mitochondrial membrane potential, giving a metric for mitochondrial function. In addition, the cells will be stained with MitoTracker Green®, which can be used to assess mitochondrial morphology. Mitochondrial morphology will be quantified in a non-biased fashion using a mathematical image analysis algorithm.
- After extraction of genomic DNA, total cellular mitochondrial biomass and mitochondrial DNA damage will be measured using traditional and long-patch quantitative polymerase chain reaction (PCR).
Myocardial tissue will be also collected prior to closure of the atriotomy. Samples will be placed into 3% buffered glutaraldehyde at the time of biopsy, and imaging of mitochondrial structure using electron microscopy will be performed.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo (0.9% Saline) | Placebo comparator | Drug: 0.9% NaCl0.9% Saline: bolus dose of 0.125mL/kg infused over 10 minutes, followed by a continuous infusion (CI) dose at 0.15mL/kg/hr for the duration of surgery. |
| Dexmedetomidine | Experimental | Drug: DexmedetomidineDexmedetomidine: bolus dose of 0.5 mcg/kg infused over 10 minutes, followed by a continuous infusion (CI) dose at 0.6 mcg/kg/hr for the duration of surgery. |
Who may qualify
- Ages
- 3 to 36 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- aged between 3 - 36 months
- having primary corrective heart surgery
Key exclusion criteria (9 listed)
- recent surgery (< 3 months)
- previous chemotherapy
- previous transfusion of blood products
- neurodevelopmental disorders (including Trisomy 21)
- supplemental oxygen requirement (< 3 months)
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 |
|---|---|---|
| DexmedetomidineAlso: PrecedexA bolus dose of 0.5 mcg/kg infused over 10 minutes will be administered, followed by a continuous infusion for the duration of the surgery at 0.6 mcg/kg/hr. | Drug | Dexmedetomidine |
| 0.9% NaClAlso: Normal Saline | Drug | Placebo (0.9% Saline) |
Primary outcome
Mitochondrial function (use high content imaging (HCI)
Time frame: Intraoperative
The primary outcomes for mitochondria will be grouped into mitochondrial function, morphology, content and mtDNA damage.
3 secondary outcomes
Creatinine level (Marker of acute renal injury)
Time frame: Postoperative day 1
Cardiac function (Left ventricular ejection fraction measured by trans-thoracic echocardiography)
Time frame: Postoperative day 1
Inotropes and vasopressors (Duration and dose of inotropes and vasopressors after surgery)
Time frame: Postoperative day 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2018.
- Individual participant dataSharing planned: No
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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.
James D O'Leary, MBBCh 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 4 study testing Dexmedetomidine and 0.9% NaCl in people with Complication of Anesthesia and Ischaemia-reperfusion 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 2 inclusion and 9 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 9 May 2018. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 James D O'Leary, MBBCh ((416) 813-1500 ext. 228845, james.oleary@sickkids.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mitochondrial function (use high content imaging (HCI) (time frame: Intraoperative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 May 2018.