Pulmonary HypertensionPhase 1NCT02120339
Carvedilol PAH A Pilot Study of Efficacy and Safety
A Phase 1 study testing Carvedilol in people with Pulmonary Hypertension and Cardiac MRI <40, run by University of Minnesota at 1 site in United States.
Trial summary
Estimate the effect of chronic beta-adrenergic receptor blockade with carvedilol on RV function in patients with PAH. Assess the safety and tolerability of chronic carvedilol therapy in patients with PAH Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Pulmonary Hypertension, Cardiac MRI <40
- What is being tested?
- Carvedilol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Jun 2016
- Phase
- Phase 1
- 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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects will be eligible to participate in the study if all of the following conditions exist:
- Age > 18 years
- WHO category 1 pulmonary arterial hypertension (Dana Point 2008)
- WHO functional class II-III
- RVEF by cardiac MRI < 40%
- Mean pulmonary artery pressure > 40 mm Hg
- Stable on PAH-specific therapy as defined by no change in PAH-specific treatment and functional class in the past 3 months. Patient can be on either mono or combination PAH-specific therapy
Who cannot join
- 1. Subjects will be excluded from participation in the study if any of the following conditions exist: 2. Significant persistent bradycardia (resting heart rate < 60 bpm) without a permanent pacemaker 3. Second or third degree AV block without a permanent pacemaker 4. Significant sinus tachycardia (resting heart rate > 100 bpm) 5. Use of anti-arrhythmic drugs 6. Hypotension defined as systolic blood pressure < 100 mmHg at the time of enrollment 7. Significant illness in the past 30 days requiring hospitalization 8. Acute decompensated right heart failure within past 30 days 9. Known allergy or intolerance to carvedilol or other β blockers 10. Cardiac index < 2 l/min/m2 or right atrial pressure > 15 mm Hg 11. Asthma
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55414
About this study
Official title: Beta Blockers in Pulmonary Arterial Hypertension (PAH) A Pilot Study of Efficacy and Safety
Estimate the effect of chronic beta-adrenergic receptor blockade with carvedilol on RV function in patients with PAH.
Assess the safety and tolerability of chronic carvedilol therapy in patients with PAH
Read the detailed description
This is a prospective, open label, uncontrolled, pilot study examining the safety and efficacy of beta-blocker therapy with carvedilol on RV function in stable PAH Patients with World Health Organization (WHO) functional class II or III symptoms and RV ejection fraction (EF) < 40%. Twenty-five evaluable patients will be enrolled at the University of Minnesota.
Specific Aims:
1.1 Primary Efficacy Endpoint: Adult males and females on a stable dose of an approved PAH medication will undergo cardiac magnetic resonance imaging (MRI), right heart catheterization (RHC), echocardiogram, 6-minute walk test (6-MWT), measurement of plasma NT-ProBNP and serum catecholamine, and quality of life assessment. Patients will receive carvedilol (3.25 mg/kg bid escalating to 25 mg/kg bid over 3 months). Testing is repeated at the end of the study (month 6). RVEF measured by cardiac MRI is the primary efficacy endpoint. We define a 5% increase in RVEF as a meaningful change.
- Conditions
- Pulmonary Hypertension, Cardiac MRI <40
- Being tested
- Carvedilol
- Keywords
- Hypertension, PAH
- Medical subject headings
- Hypertension, Pulmonary, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
| Study group | Role | What they receive |
|---|---|---|
| Carvedilol | Experimental | Carvedilol 0-3.125 mg daily Escalating to 6.25 twice a day Receives: Drug: Carvedilol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change in RVEF
- The primary efficacy outcome is the mean change in RVEF as measured by cardiac MRI before and after 6 months of carvedilol treatment. An improvement of 5% will be considered to be clinically significant. Assessment of the RV is challenging due to its complex geometry. Cardiac MRI offers the ability to acquire 3-dimensional datasets that do not require geometric modeling. In addition to being highly reproducible40, RVEF measured by cardiac MRI can be used to identify PAH patients that are likely to have clinical worsening41. The prognostic ability of cardiac MRI-measurements of RVEF is similar to that as mean pulmonary artery pressure and exercise capacity
Measured: Baseline and 6 months
Secondary outcomes (1)
Absence of Adverse Events
The primary safety outcome is the absence of adverse events associated with carvedilol including hypotension (<90 mm Hg), bradycardia (<50 bpm or advanced atrioventricular nodal block), bronchospam, or acute decompensated right heart failure requiring hospitalization.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2014 (estimated)
- Study startMay 2014
- Primary completionJun 2015
- Study completionJun 2016
Why it stopped: Low enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe 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
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thenappan Thenappan, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02120339
- Sponsor's protocol ID
- PAH
- Status last verified
- Jul 2019
- First submitted
- 17 Apr 2014
- Last updated
- 12 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Thenappan T, Weir EK, Prins KW, Pritzker MR, Archer SL. Carvedilol for Treatment of Right Ventricular Dysfunction in Pulmonary Arterial Hypertension. J Am Heart Assoc. 2021 Jul 20;10(14):e021518. doi: 10.1161/JAHA.121.021518. Epub 2021 Jul 14. No abstract available.
PubMed 34259020
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beta Blockers in Pulmonary Arterial Hypertension (PAH) A Pilot Study of Efficacy and Safety
- ClinicalTrials.gov ID
- NCT02120339
- Acronym / sponsor ID
- PAH
- Conditions
- Pulmonary Hypertension, Cardiac MRI <40
- Keywords
- Hypertension, PAH
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 22 Apr 2014 (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.
Estimate the effect of chronic beta-adrenergic receptor blockade with carvedilol on RV function in patients with PAH.
Assess the safety and tolerability of chronic carvedilol therapy in patients with PAH
Detailed description
This is a prospective, open label, uncontrolled, pilot study examining the safety and efficacy of beta-blocker therapy with carvedilol on RV function in stable PAH Patients with World Health Organization (WHO) functional class II or III symptoms and RV ejection fraction (EF) < 40%. Twenty-five evaluable patients will be enrolled at the University of Minnesota.
Specific Aims:
1.1 Primary Efficacy Endpoint: Adult males and females on a stable dose of an approved PAH medication will undergo cardiac magnetic resonance imaging (MRI), right heart catheterization (RHC), echocardiogram, 6-minute walk test (6-MWT), measurement of plasma NT-ProBNP and serum catecholamine, and quality of life assessment. Patients will receive carvedilol (3.25 mg/kg bid escalating to 25 mg/kg bid over 3 months). Testing is repeated at the end of the study (month 6). RVEF measured by cardiac MRI is the primary efficacy endpoint. We define a 5% increase in RVEF as a meaningful change.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Carvedilol | Experimental | Drug: CarvedilolCarvedilol 0-3.125 mg daily Escalating to 6.25 twice a day |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects will be eligible to participate in the study if all of the following conditions exist:
- Age > 18 years
- WHO category 1 pulmonary arterial hypertension (Dana Point 2008)
- WHO functional class II-III
- RVEF by cardiac MRI < 40%
Key exclusion criteria (1 listed)
- 1. Subjects will be excluded from participation in the study if any of the following conditions exist: 2. Significant persistent bradycardia (resting heart rate < 60 bpm) without a permanent pacemaker 3. Second or third degree AV block without a permanent pacemaker 4. Significant sinus tachycardia (resting heart rate > 100 bpm) 5. Use of anti-arrhythmic drugs 6. Hypotension defined as systolic blood pressure < 100 mmHg at the time of enrollment 7. Significant illness in the past 30 days requiring hospitalization 8. Acute decompensated right heart failure within past 30 days 9. Known allergy or intolerance to carvedilol or other β blockers 10. Cardiac index < 2 l/min/m2 or right atrial pressure > 15 mm Hg 11. Asthma
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 |
|---|---|---|
| Carvedilol | Drug | Carvedilol |
Primary outcome
Mean change in RVEF
Time frame: Baseline and 6 months
1. The primary efficacy outcome is the mean change in RVEF as measured by cardiac MRI before and after 6 months of carvedilol treatment. An improvement of 5% will be considered to be clinically significant. Assessment of the RV is challenging due to its complex geometry. Cardiac MRI offers the ability to acquire 3-dimensional datasets that do not require geometric modeling. In addition to being highly reproducible40, RVEF measured by cardiac MRI can be used to identify PAH patients that are likely to have clinical worsening41. The prognostic ability of cardiac MRI-measurements of RVEF is similar to that as mean pulmonary artery pressure and exercise capacity
1 secondary outcome
Absence of Adverse Events
Time frame: 6 months
Results and safety
The study was stopped early (reason given: Low enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2019.
- Derived from this study: PubMed 34259020Thenappan T, Weir EK, Prins KW, Pritzker MR, Archer SL. Carvedilol for Treatment of Right Ventricular Dysfunction in Pulmonary Arterial Hypertension. J Am Heart Assoc. 2021 Jul 20;10(14):e021518. doi: 10.1161/JAHA.121.021518. Epub 2021 Jul 14. No abstract available.
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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.
Thenappan Thenappan, MD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Carvedilol in people with Pulmonary Hypertension and Cardiac MRI <40, run by University of Minnesota at 1 site in United States.
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 7 inclusion and 1 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: stopped early, as of the sponsor's last update on 12 Jul 2019. 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 United States. 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 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.
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 stopped early (reason given: Low enrollment). Results are not available in the source record.
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?
Mean change in RVEF (time frame: Baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02120339, which also lists 1 linked publication.
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 12 Jul 2019.