Congenital Heart DiseasePhase 2NCT01841177
Evaluating Precision of Therapy - Milrinone
A Phase 2 study testing Milrinone in people with Congenital Heart Disease, run by The Hospital for Sick Children at 2 sites in Canada.
Trial summary
Children with congenital heart disease have significant morbidity including low cardiac output syndrome and subsequent organ dysfunction that may be prevented by optimization of circulatory function. More than half of these children receive milrinone. Read more about this study
- Who is it for?
- Ages 1 day to 18 years
- Conditions the study is for
- Congenital Heart Disease
- What is being tested?
- Milrinone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 2 sitesCanada
- Study dates
- Apr 2013to Aug 2020
- Phase
- Phase 2
- 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 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Admitted to a Pediatric (0 - 18 years) Intensive Care Unit following cardiopulmonary bypass (CPB) and surgery for congenital heart disease.
- Clinical decision by treating team to start milrinone infusion.
- Anticipated to receive milrinone infusion for more than 24hs. This limit will increase the proportion of sicker children in the sample, increasing the power of the study.
- Has an arterial line, and a central venous line defined as radiologically confirmed line
- Informed consent obtained
Who cannot join
- Premature infants (<36 weeks post-conceptual age) or weight less than 2.0 kg.
- Failure to provide consent
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
Children with congenital heart disease have significant morbidity including low cardiac output syndrome and subsequent organ dysfunction that may be prevented by optimization of circulatory function. More than half of these children receive milrinone. Clinical evaluation cannot distinguish between patients with sub-therapeutic, therapeutic, and toxic milrinone drug levels. Consequently children who require pharmacologic circulatory support may be receiving sub-optimal dosing, and children who do not need milrinone may be receiving milrinone unnecessarily. The primary objective of this study is to determine if optimizing milrinone levels with therapeutic drug monitoring in critically ill children following cardiac surgery improves clinical outcomes and reduces the duration of milrinone infusion. This study hypothesizes that optimizing milrinone levels with therapeutic drug monitoring in critically ill children following cardiac surgery will improve clinical outcomes and reduce the duration of milrinone infusion.
Read the detailed description
The proposed trial is a pilot of an open label, randomized trial of milrinone therapeutic drug monitoring in patients < 18 years treated with milrinone following open-heart surgery for congenital heart disease at the Hospital for Sick Children, Toronto. We will randomize patients to (1) receiving therapeutic drug monitoring or (2) control patients who receive standard care. Standard care involves titration of milrinone infusion based on clinical examination by the treating team. Control patients will have milrinone plasma levels drawn but not analysed until the end of the study. The intervention is (1) regular measurement of milrinone levels; and (2) physician feedback of plasma levels in experimental arm by the ICU pharmacist. After obtaining consent, eligible subjects will be allocated to a trial group by random assignment (sealed envelopes) within 3 strata in a 1:1 allocation. These strata are < 2 years, 2- 10 years and > 10 years to ensure equal distribution of these age ranges in each group for pharmacokinetic analysis. For the intervention group, sampling for milrinone levels will occur at 0 hours (upon arrival to ICU with routine admission blood collection) and approximately every 6- 8 hours (whenever the line is accessed for routine blood work). The last sample will be taken 6-8 hours after cessation of infusion, or if the patient leaves the ICU, or the maximum amount of blood sampling has been reached or after 7 days for children weighing more than 8 kgs (or 5 days for children weighing less than 8 kgs), which ever comes first. Follow-up will be exclusively during the period of hospitalization in the ICU until ICU discharge. An optional algorithm with a proposed titration for milrinone will be provided for use at the discretion of the treating team. Clinical outcomes will be measured as a composite outcome of dysrhythmia, LCOS and death.
- Conditions
- Congenital Heart Disease
- Being tested
- Milrinone
- Keywords
- Congenital Heart Disease, Pediatrics, Milrinone, Cardiopulmonary Bypass, Therapeutic Drug Monitoring
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MilrinoneDrug
Also called Milrinone Lactate Inj
Milrinone is a potent selective phosphodiesterase (PDE) type III inhibitor which stimulates myocardial function (inotropy), causes peripheral vasodilatation (afterload reduction) and improves myocardial relaxation (lusitropy).
| Study group | Role | What they receive |
|---|---|---|
| Therapeutic Drug Monitoring | Experimental | The intervention is [1] regular measurement of milrinone levels; [2]physician feedback of plasma levels in experimental arm by the ICU pharmacist ( this process currently occurs for other drugs such as vancomycin). Receives: Drug: Milrinone |
| Standard Care | Active comparator | Standard care involves titration of milrinone infusion based on clinical examination by the treating team. The control group will receive standard care: with milrinone dose modification on clinical assessment. Control patients will have milrinone plasma levels drawn but not analysed until the end of the study. Receives: Drug: Milrinone |
What is being measured
The primary outcome is the main question the study is designed to answer.
LCOS,
Composite outcome
Measured: within first 48 hours
Secondary outcomes (4)
Therapeutic Levels
Therapeutic levels at 8-16 hours post CPB measured in ng/mL [to coincide with recognized nadir in CO post cardiopulmonary bypass]
Measured: +8, +16 hours
Duration
Duration of milrinone infusion (number of hours in the week)
Measured: Duration of ICU stay or maximum of 1 week
Dosage Adjustment
Number of dosage adjustments in control and experimental group after clinical assessment
Measured: Duration of infusion or maximum of 1 week
Plasma Milrinone Levels
Plasma milrinone levels in both groups
Measured: Duration of infusion or maximum of 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2013 (estimated)
- Study startApr 2013
- Primary completionAug 2020
- Study completionAug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Heart DiseaseStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Katherine Taylor, The Hospital for Sick Children
- Investigators
- Katherine Taylor, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01841177
- Sponsor's protocol ID
- 1000032365
- Status last verified
- Dec 2021
- First submitted
- 23 Apr 2013
- Last updated
- 6 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating Precision of Therapy - Milrinone
- ClinicalTrials.gov ID
- NCT01841177
- Acronym / sponsor ID
- 1000032365
- Conditions
- Congenital Heart Disease
- Keywords
- Congenital Heart Disease, Pediatrics, Milrinone, Cardiopulmonary Bypass, Therapeutic Drug Monitoring
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- Aug 2020 (actual)
- Study completion
- Aug 2020 (actual)
- First posted
- 26 Apr 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.
Children with congenital heart disease have significant morbidity including low cardiac output syndrome and subsequent organ dysfunction that may be prevented by optimization of circulatory function. More than half of these children receive milrinone. Clinical evaluation cannot distinguish between patients with sub-therapeutic, therapeutic, and toxic milrinone drug levels. Consequently children who require pharmacologic circulatory support may be receiving sub-optimal dosing, and children who do not need milrinone may be receiving milrinone unnecessarily. The primary objective of this study is to determine if optimizing milrinone levels with therapeutic drug monitoring in critically ill children following cardiac surgery improves clinical outcomes and reduces the duration of milrinone infusion. This study hypothesizes that optimizing milrinone levels with therapeutic drug monitoring in critically ill children following cardiac surgery will improve clinical outcomes and reduce the duration of milrinone infusion.
Detailed description
The proposed trial is a pilot of an open label, randomized trial of milrinone therapeutic drug monitoring in patients < 18 years treated with milrinone following open-heart surgery for congenital heart disease at the Hospital for Sick Children, Toronto. We will randomize patients to (1) receiving therapeutic drug monitoring or (2) control patients who receive standard care. Standard care involves titration of milrinone infusion based on clinical examination by the treating team. Control patients will have milrinone plasma levels drawn but not analysed until the end of the study. The intervention is (1) regular measurement of milrinone levels; and (2) physician feedback of plasma levels in experimental arm by the ICU pharmacist. After obtaining consent, eligible subjects will be allocated to a trial group by random assignment (sealed envelopes) within 3 strata in a 1:1 allocation. These strata are < 2 years, 2- 10 years and > 10 years to ensure equal distribution of these age ranges in each group for pharmacokinetic analysis. For the intervention group, sampling for milrinone levels will occur at 0 hours (upon arrival to ICU with routine admission blood collection) and approximately every 6- 8 hours (whenever the line is accessed for routine blood work). The last sample will be taken 6-8 hours after cessation of infusion, or if the patient leaves the ICU, or the maximum amount of blood sampling has been reached or after 7 days for children weighing more than 8 kgs (or 5 days for children weighing less than 8 kgs), which ever comes first. Follow-up will be exclusively during the period of hospitalization in the ICU until ICU discharge. An optional algorithm with a proposed titration for milrinone will be provided for use at the discretion of the treating team. Clinical outcomes will be measured as a composite outcome of dysrhythmia, LCOS and death.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Therapeutic Drug Monitoring | Experimental | Drug: MilrinoneThe intervention is [1] regular measurement of milrinone levels; [2]physician feedback of plasma levels in experimental arm by the ICU pharmacist ( this process currently occurs for other drugs such as vancomycin). |
| Standard Care | Active comparator | Drug: MilrinoneStandard care involves titration of milrinone infusion based on clinical examination by the treating team. The control group will receive standard care: with milrinone dose modification on clinical assessment. Control patients will have milrinone plasma levels drawn but not analysed until the end of the study. |
Who may qualify
- Ages
- 1 day to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Admitted to a Pediatric (0 - 18 years) Intensive Care Unit following cardiopulmonary bypass (CPB) and surgery for congenital heart disease.
- Clinical decision by treating team to start milrinone infusion.
- Anticipated to receive milrinone infusion for more than 24hs. This limit will increase the proportion of sicker children in the sample, increasing the power of the study.
- Has an arterial line, and a central venous line defined as radiologically confirmed line
- Informed consent obtained
Key exclusion criteria (2 listed)
- Premature infants (<36 weeks post-conceptual age) or weight less than 2.0 kg.
- Failure to provide consent
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 |
|---|---|---|
| MilrinoneAlso: Milrinone Lactate InjMilrinone is a potent selective phosphodiesterase (PDE) type III inhibitor which stimulates myocardial function (inotropy), causes peripheral vasodilatation (afterload reduction) and improves myocardial relaxation (lusitropy). | Drug | Standard Care, Therapeutic Drug Monitoring |
Primary outcome
LCOS,
Time frame: within first 48 hours
Composite outcome
4 secondary outcomes
Therapeutic Levels
Time frame: +8, +16 hours
Duration
Time frame: Duration of ICU stay or maximum of 1 week
Dosage Adjustment
Time frame: Duration of infusion or maximum of 1 week
Plasma Milrinone Levels
Time frame: Duration of infusion or maximum of 1 week
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 6 Jan 2022.
- 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.
Katherine Taylor, MD principal investigator
The Hospital for Sick Children
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Milrinone in people with Congenital Heart Disease, run by The Hospital for Sick Children at 2 sites 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 5 inclusion and 2 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 6 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
LCOS, (time frame: within first 48 hours). 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 6 Jan 2022.