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Evaluating Precision of Therapy - Milrinone

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ClinicalTrials.gov Identifier: NCT01841177
Recruitment Status : Unknown
Verified May 2016 by Katherine Taylor, The Hospital for Sick Children.
Recruitment status was:  Recruiting
First Posted : April 26, 2013
Last Update Posted : May 13, 2016
Sponsor:
Information provided by (Responsible Party):
Katherine Taylor, The Hospital for Sick Children

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Congenital Heart Disease Drug: Milrinone Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluating Precision of Therapy - Milrinone
Study Start Date : April 2013
Estimated Primary Completion Date : August 2017
Estimated Study Completion Date : August 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Diseases

Arm Intervention/treatment
Experimental: Therapeutic Drug Monitoring
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).
Drug: Milrinone
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).
Other Name: Milrinone Lactate Inj

Active Comparator: Standard Care
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.
Drug: Milrinone
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).
Other Name: Milrinone Lactate Inj




Primary Outcome Measures :
  1. Dysrhythmia, LCOS, and Death [ Time Frame: Duration of ICU stay or maximum of 1 week ]
    Composite outcome


Secondary Outcome Measures :
  1. Therapeutic Levels [ Time Frame: +8, +16 hours ]
    Therapeutic levels at 8-16 hours post CPB measured in ng/mL [to coincide with recognized nadir in CO post cardiopulmonary bypass]

  2. Duration [ Time Frame: Duration of ICU stay or maximum of 1 week ]
    Duration of milrinone infusion (number of hours in the week)

  3. Dosage Adjustment [ Time Frame: Duration of infusion or maximum of 1 week ]
    Number of dosage adjustments in control and experimental group after clinical assessment

  4. Plasma Milrinone Levels [ Time Frame: Duration of infusion or maximum of 1 week ]
    Plasma milrinone levels in both groups



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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Premature infants (<36 weeks post-conceptual age) or weight less than 2.0 kg.
  • Failure to provide consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01841177


Contacts
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Contact: Katherine Taylor, MD (416)813-7654 ext 202453 katherine.taylor@sickkids.ca

Locations
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Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Katherine Taylor       katherine.taylor@sickkids.ca   
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Katherine Taylor, MD    (416)813-7654 ext 202453    katherine.taylor@sickkids.ca   
Sub-Investigator: Christopher Parshuram, MD         
Sub-Investigator: Steven Schwartz, MD         
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
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Principal Investigator: Katherine Taylor, MD The Hospital for Sick Children

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Responsible Party: Katherine Taylor, Staff Anesthesiologist, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT01841177     History of Changes
Other Study ID Numbers: 1000032365
First Posted: April 26, 2013    Key Record Dates
Last Update Posted: May 13, 2016
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Katherine Taylor, The Hospital for Sick Children:
Congenital Heart Disease
Pediatrics
Milrinone
Cardiopulmonary Bypass
Therapeutic Drug Monitoring

Additional relevant MeSH terms:
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Heart Diseases
Heart Defects, Congenital
Cardiovascular Diseases
Congenital Abnormalities
Cardiovascular Abnormalities
Milrinone
Cardiotonic Agents
Platelet Aggregation Inhibitors
Vasodilator Agents
Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs