Pulmonary Arterial HypertensionPhase 1/2NCT01723371
Beta Blockers for Treatment of Pulmonary Arterial Hypertension in Children
A Phase 1/2 study testing Carvedilol in people with Pulmonary Arterial Hypertension, run by The Hospital for Sick Children at 1 site in Canada.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 8 to 17 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Carvedilol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2012to Sep 2015
- Phase
- Phase 1/2
- 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 8 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients must be ≥ 8 and ≤ 17.5 years of age at the time of study enrollment.
- Patients must have a mean pulmonary artery pressure of greater than 25mmHg at rest in a setting of normal pulmonary arterial wedge pressure of 15mmHg or less with a PVR index greater than 3 Woods units•m2 at last hemodynamic study.
- Patients must be diagnosed with any of the following:Idiopathic PAH (IPAH), PAH associated with repaired congenital heart disease, PAH associated with minor congenital heart disease (small interventricular communication, small interarterial communication, small ductus arteriosis)
- Patients must be clinically stable (i.e. no treatment changes) for the last 3 months
- Patients must have no or minimal evidence of fluid overload or volume depletion judged by clinical evaluation (with or without diuretic treatment)
- Written informed consent
Who cannot join
- Patients who are unable to perform a six minute walk test (6MWT)
- Patients with a known history of pulmonary hypertension secondary to venoocclusive disease and/or capillary hemangiomatosis; pulmonary hypertensions owing to left heart disease
- Patients who have previously received treatment with an intravenous positive inotropic agent in the last 3 months
- Patients who are currently receiving β-blockers
- Patients with a known history of reactive airways disease (bronchial asthma or relate bronchospastic conditions)
- Patients with chronic obstructive pulmonary disease (COPD)
Show all 18Show fewer
- Patients with a known history of adverse reaction to β-blockers
- Patients with a heart block on ECG or resting heart rate < 60 bpm
- Patients with systemic hypotension (below 5th percentile for age) are not eligible as follows: 1-10 years old: systolic blood pressure defined as < [70 + (2 x age in years)] mmHg; Older than 10 years: systolic blood pressure < 90 mmHg
- Patients with coagulopathy (INR < 1.5 or platelet count <50,000/mm3)
- Patients with a known history of severe hepatic impairment (defined by the presence of ascites, esophageal varices, jaundice or spider angiomata)
- Patients with severe renal insufficiency (defined as creatinine clearance < 30 mL/min/m2)
- Patients with a known malignancy or other co-morbidity expected to limit survival or to limit the ability to complete the study
- Patients with trisomy 21
- Patients with a known history of sick sinus syndrome
- Patients with a known history of moderate or severe primary obstructive valvular heart disease
- Patients with a known history of diabetes
- Female patients who are pregnant of breast-feeding
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Carvedilol
- Keywords
- Pulmonary Arterial Hypertension (PAH, Pediatrics, Right Heart Failure (RHF), Carvedilol, Beta-blockers
- Medical subject headings
- Pulmonary Arterial Hypertension, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Carvedilol | Experimental | Not described Receives: Drug: Carvedilol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events
-Incidence of major adverse effects defined as bradycardia, hypotension, and syncope, worsening of symptoms, disease state and death
Measured: Throughout study (Baseline to week 31)
Secondary outcomes (3)
Improvement in the six minute walk test (6MWT) and cardiopulmonary exercise testing (CPX)
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.
Measured: Change over 6 months
Improvement in echocardiogram and magnetic resonance imaging (MRI) parameters
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.
Measured: Change over 6 months
Feasibility of carvedilol
- 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
Measured: Baseline, Week 0, 2, 3, 4, 5, 6, 10, 18, 22, 30, 31
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2012 (estimated)
- Study startSep 2012
- Primary completionSep 2015
Why it stopped: Due to lack of enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mark Friedberg, The Hospital for Sick Children
- Investigators
- Mark Friedberg, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01723371
- Sponsor's protocol ID
- 1000031903
- Status last verified
- Dec 2015
- First submitted
- 31 Oct 2012
- Last updated
- 31 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beta Blockers for Treatment of Pulmonary Arterial Hypertension in Children
- ClinicalTrials.gov ID
- NCT01723371
- Acronym / sponsor ID
- 1000031903
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- Pulmonary Arterial Hypertension (PAH, Pediatrics, Right Heart Failure (RHF), Carvedilol, Beta-blockers
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Due to lack of enrollment.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Sep 2015 (actual)
- First posted
- 7 Nov 2012 (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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carvedilol | Experimental | Drug: Carvedilol |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Patients must be ≥ 8 and ≤ 17.5 years of age at the time of study enrollment.
- Patients must have a mean pulmonary artery pressure of greater than 25mmHg at rest in a setting of normal pulmonary arterial wedge pressure of 15mmHg or less with a PVR index greater than 3 Woods units•m2 at last hemodynamic study.
- Patients must be diagnosed with any of the following:Idiopathic PAH (IPAH), PAH associated with repaired congenital heart disease, PAH associated with minor congenital heart disease (small interventricular communication, small interarterial communication, small ductus arteriosis)
- Patients must be clinically stable (i.e. no treatment changes) for the last 3 months
- Patients must have no or minimal evidence of fluid overload or volume depletion judged by clinical evaluation (with or without diuretic treatment)
Key exclusion criteria (18 listed)
- Patients who are unable to perform a six minute walk test (6MWT)
- Patients with a known history of pulmonary hypertension secondary to venoocclusive disease and/or capillary hemangiomatosis; pulmonary hypertensions owing to left heart disease
- Patients who have previously received treatment with an intravenous positive inotropic agent in the last 3 months
- Patients who are currently receiving β-blockers
- Patients with a known history of reactive airways disease (bronchial asthma or relate bronchospastic conditions)
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 |
|---|---|---|
| CarvedilolCarvedilol 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. | Drug | Carvedilol |
Primary outcome
Incidence of Adverse Events
Time frame: Throughout study (Baseline to week 31)
-Incidence of major adverse effects defined as bradycardia, hypotension, and syncope, worsening of symptoms, disease state and death
3 secondary outcomes
Improvement in the six minute walk test (6MWT) and cardiopulmonary exercise testing (CPX)
Time frame: Change over 6 months
Improvement in echocardiogram and magnetic resonance imaging (MRI) parameters
Time frame: Change over 6 months
Feasibility of carvedilol
Time frame: Baseline, Week 0, 2, 3, 4, 5, 6, 10, 18, 22, 30, 31
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2015.
Related trials for Pulmonary Arterial Hypertension
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
Pulmonary Arterial Hypertension
RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
Pulmonary Disease, Pulmonary Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH
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.
Mark Friedberg, MD 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 1/2 study testing Carvedilol in people with Pulmonary Arterial Hypertension, 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 6 inclusion and 18 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: withdrawn, as of the sponsor's last update on 31 Dec 2015. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was withdrawn before enrolling participants, so there are no results.
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?
Incidence of Adverse Events (time frame: Throughout study (Baseline to week 31)). 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 31 Dec 2015.