Beta Blockers for Treatment of Pulmonary Arterial Hypertension in Children
This study will determine the safety and feasibility of using a β-blocker (in this case carvedilol) in the treatment of pediatric patients with Left Heart Failure (LHF) in children with Pulmonary Arterial Hypertension (PAH). Carvedilol affects the nervous system, the same system that is highly activated in response to stress in patients with PAH. Each patient is administered a dosage of carvedilol, according to their weight. This dosage is increased incrementally over the span of the study, if the patient responds well to the drug. The study will determine whether the potential adverse side effects of carvedilol outweigh the possible positive results in reducing LHF. The hypothesis of this study predicts that carvedilol will have positive effects in treating LHF, similar to their use in treatment of Right Heart Failure (RHF). This is a single-centered pilot study. Each patient will be studied for approximately 31 weeks.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Beta Blockers for Treatment of Pulmonary Arterial Hypertension in Children|
- Incidence of Adverse Events [ Time Frame: Throughout study (Baseline to week 31) ] [ Designated as safety issue: Yes ]-Incidence of major adverse effects defined as bradycardia, hypotension, and syncope, worsening of symptoms, disease state and death
- Improvement in the six minute walk test (6MWT) and cardiopulmonary exercise testing (CPX) [ Time Frame: Change over 6 months ] [ Designated as safety issue: No ]This will be measured by the difference in walking distance in the 6MWT and peak oxygen consumption in the CPX, between the baseline condition before the study and after 6 months with maintenance dose of carvedilol.
- Improvement in echocardiogram and magnetic resonance imaging (MRI) parameters [ Time Frame: Change over 6 months ] [ Designated as safety issue: No ]The echocardiogram will be a subjective assessment of the right valve (RV) fractional area of change through TAPSE. The MRI will measure the RV ejection fraction. Both indicators will measure the different between the baseline condition before the study and after 6 months with maintenance dose of carvedilol.
- Feasibility of carvedilol [ Time Frame: Baseline, Week 0, 2, 3, 4, 5, 6, 10, 18, 22, 30, 31 ] [ Designated as safety issue: No ]
- Proportion of patients achieving target maintenance dose of carvedilol
- Proportion of patients requiring dose adjustment due to bradycardia and/or hypertension
- Proportion of patients stopping treatment with carvedilol due to serious adverse events
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||September 2017|
|Estimated Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
Carvedilol will be administered orally. The initial dose of carvedilol will be 0.05mg/kg/day divided into 2 doses. After two weeks, at subsequent weekly study visits, the dose of carvedilol will be increased incrementally to 0.1mg/kg in Week 2, 0.2mg/kg in Week 3, 0.4mg/kg in Week 4, 0.6mg/kg in Week 5, and 0.8mg/kg in Week 6, when the target dose of 0.8mg/kg/day (if weight is less than 62.5kg) or 50mg/day (if weight is greater than 62.5kg) is achieved. This dosage, assuming no adverse effects, will be maintained between Weeks 6 and 30 of the study. After the maintenance period from Week 6 to 30, patients will be weaned over 5 to 7 days or continued on a non-study drug supply.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01723371
|Contact: Mark Friedberg, MD||(416)firstname.lastname@example.org|
|The Hospital for Sick Children||Recruiting|
|Toronto, Ontario, Canada, M5G 1X8|
|Contact: Mark Friedberg, MD (416)813-7239 email@example.com|
|Principal Investigator: Mark Friedberg, MD|
|Sub-Investigator: Andrew Redington, MD|
|Sub-Investigator: Tilman Humpl, MD|
|Sub-Investigator: Jennifer Russell, MD|
|Sub-Investigator: Shi-Joon Yoo, MD|
|Sub-Investigator: Janette T. Reyes, NP|
|Principal Investigator:||Mark Friedberg, MD||The Hospital for Sick Children|