Evaluating Precision of Therapy - Milrinone
Condition: Congenital Heart Disease
MeSH terms: Heart Diseases; Heart Defects, Congenital
Study type: Interventional
Phase: Phase 2

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.
    

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.
    

Intervention name(s): Milrinone
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): Milrinone Lactate Inj
Intervention MeSH terms: Milrinone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Congenital Heart Disease; Pediatrics; Milrinone; Cardiopulmonary Bypass; Therapeutic Drug Monitoring