Pulmonary HypertensionPAHTCHNCT01586156
PAHTCH Pulmonary Arterial Hypertension Treatment With Carvedilol for Heart Failure (Carvedilol)
A study testing Carvedilol in people with Pulmonary Hypertension, run by The Cleveland Clinic at 1 site in United States.
Trial summary
Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature leading to elevated pulmonary pressure and right ventricular (RV) dysfunction with heart failure. Measures of RV function are better predictors of mortality and long term outcomes than pulmonary vascular resistance. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- Carvedilol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2012to Jul 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women age 18 or older not greater than age 65 years
- Diagnosis of pulmonary arterial hypertension class 1, 3, 4, 5 (Dana Point 2008)
- NYHA (New York Health Association)/WHO (World Health Organization) Class I-III
- PAH medications must have been initiated according to the latest consensus statement recommendations and remained stable for the last 30 days
- Women of child-bearing age must use a double-barrier local contraception till completion of the study
- Subjects must demonstrate understanding of the study, sign the informed consent, and have a reliable method of communication for contact and ability to comply with the study requirements
Who cannot join
- Participation in any other treatment studies during enrollment
- Significant illness in the past 30 days requiring hospitalization
- Hepatic insufficiency (transaminase levels > 4 fold the upper limit of normal or bilirubin > 2 fold the upper limit of normal),
- History of HIV, Hepatitis B or C
- Serum creatinine > 2.8 mg/dl
- Pregnancy, breast-feeding, or lack of safe contraception
Show all 13Show fewer
- Acute decompensated heart failure within past 30 days
- Known allergy or intolerance to carvedilol or other β blockers
- Significant, persistent bradycardia (resting heart rate < 50 bpm) or hypotension (systolic blood pressure < 100 mmHg or mean blood pressure < 70 mmHg) at the time of enrollment
- Second or third-degree AV (Atrial Ventricular) block without pacemaker
- Use of CYP2D6 isoenzyme inhibitors (such as quinidine, fluoxetine, paroxetine, propafenone) which increase drug levels and result in greater vasodilating effects and hypotension
- Use of hypotensive drugs that deplete catecholamines (such as reserpine and monoamine oxidase inhibitors) which may lead to greater signs of hypotension or bradycardia
- Other medical and psychosocial conditions as determined by principal investigator deemed unsuitable for enrollment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pulmonary Arterial Hypertension Treatment With Carvedilol for Heart Failure
Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature leading to elevated pulmonary pressure and right ventricular (RV) dysfunction with heart failure. Measures of RV function are better predictors of mortality and long term outcomes than pulmonary vascular resistance. The interaction between RV function and the pulmonary circulation is not fully understood, but increased after load appears insufficient to explain right heart failure. Yet, all approved PAH therapies target vasodilation of the pulmonary vasculature to lower pressures
Read the detailed description
Pulmonary arterial hypertension (PAH) is a serious condition characterized by endothelial dysfunction leading to pulmonary vascular constriction, smooth muscle and endothelial proliferation, and progressive right-sided heart failure. The severity of pulmonary hypertension is mostly determined by the response of the right ventricle (RV) to the increased afterload or pulmonary pressures, and RV failure is the leading cause of death in PAH. Most accepted therapies for PAH have been aimed at vasodilation of the pulmonary vasculature, and there has been little thought that PAH patients would benefit from traditional left heart failure treatments. A cornerstone therapy in left heart failure is £]-adrenergic receptor blockade because of its ability to reverse cardiac remodeling and improve clinical outcomes, despite decades of concern regarding its propensity to exacerbate heart failure. It has been reported to reduce mortality by about 30% in patients, and while the precise mechanisms that contribute to its beneficial effects remain to be elucidated, there is evidence that patients with underlying contractile reserve (i.e., via recruitment of viable myocardium with £]-adrenergic receptor stimulation) may experience greater recovery of their cardiac function. In a study using rats with pulmonary hypertension treated with £] blocker, RV function improved, and maladaptive myocardial remodeling was prevented.
- Conditions
- Pulmonary Hypertension
- Being tested
- Carvedilol, placebo
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
Also called low fixed dose, escalating dose
Group 1 will receive 3.125mg carvedilol twice daily for six months.Group 2 will receive carvedilol in a dose escalation scheme.
placeboDrug
Placebo will be taken twice daily for 6 months
| Study group | Role | What they receive |
|---|---|---|
| Open Label Carvedilol | Active comparator | Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU (Clinical Research Unit) for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months.Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. Receives: Drug: Carvedilol |
| Placebo Arm | Placebo comparator | Eligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac Glucose Uptake in FDG-PET (Fluorodeoxyglucose-Positron Emission Tomography)
We hypothesize that use of carvedilol in patients with PAH (Pulmonary Arterial Hypertension) will decrease the cardiac glucose utilization, and this will be measurable as a drop in fasting FDG-PET standardized uptake values of the heart at 6 months as compared to baseline
Measured: 6 months
Secondary outcomes (2)
Urinary cAMP (Cyclic Adenosine Monophosphate)/Creatinine
We hypothesize that use of carvedilol in patients with PAH will increase beta adrenergic receptor function and this will be measurable as an increase in cAMP measured in the urine at 6 months in participants in dose escalation carvedilol.
Measured: 6 months
Beta-Adrenergic Receptor (Alprenolol Binding Assay)
We hypothesize that use of carvedilol in patients with PAH will increase beta- adrenergic receptor availability, and this will be measurable as a increase in alprenolol binding over time of drug use.
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 posted26 Apr 2012 (estimated)
- Study startDec 2012
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)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 The Cleveland ClinicThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Samar Farha, MD, The Cleveland Clinic
- Investigators
- Serpil Erzurum, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01586156
- Sponsor's protocol ID
- 11-1198
- Other IDs
- R01HL115008
- Acronym
- PAHTCH
- Status last verified
- Nov 2018
- First submitted
- 23 Apr 2012
- Last updated
- 5 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Farha S, Saygin D, Park MM, Cheong HI, Asosingh K, Comhair SA, Stephens OR, Roach EC, Sharp J, Highland KB, DiFilippo FP, Neumann DR, Tang WHW, Erzurum SC. Pulmonary arterial hypertension treatment with carvedilol for heart failure: a randomized controlled trial. JCI Insight. 2017 Aug 17;2(16):e95240. doi: 10.1172/jci.insight.95240. eCollection 2017 Aug 17.
PubMed 28814664Saygin D, Highland KB, Farha S, Park M, Sharp J, Roach EC, Tang WHW, Thomas JD, Erzurum SC, Neumann DR, DiFilippo FP. Metabolic and Functional Evaluation of the Heart and Lungs in Pulmonary Hypertension by Gated 2-[18F]-Fluoro-2-deoxy-D-glucose Positron Emission Tomography. Pulm Circ. 2017 Apr-Jun;7(2):428-438. doi: 10.1177/2045893217701917. Epub 2017 Mar 10.
PubMed 28597761Park JH, Park MM, Farha S, Sharp J, Lundgrin E, Comhair S, Tang WH, Erzurum SC, Thomas JD. Impaired Global Right Ventricular Longitudinal Strain Predicts Long-Term Adverse Outcomes in Patients with Pulmonary Arterial Hypertension. J Cardiovasc Ultrasound. 2015 Jun;23(2):91-9. doi: 10.4250/jcu.2015.23.2.91. Epub 2015 Jun 26.
PubMed 26140151Stephens OR, Weiss K, Frimel M, Rose JA, Sun Y, Asosingh K, Farha S, Highland KB, Prasad SVN, Erzurum SC. Interdependence of hypoxia and beta-adrenergic receptor signaling in pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2019 Sep 1;317(3):L369-L380. doi: 10.1152/ajplung.00015.2019. Epub 2019 Jun 26.
PubMed 31242023Cheong HI, Farha S, Park MM, Thomas JD, Saygin D, Comhair SAA, Sharp J, Highland KB, Tang WHW, Erzurum SC. Endothelial Phenotype Evoked by Low Dose Carvedilol in Pulmonary Hypertension. Front Cardiovasc Med. 2018 Dec 12;5:180. doi: 10.3389/fcvm.2018.00180. eCollection 2018.
PubMed 30619887
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pulmonary Arterial Hypertension Treatment With Carvedilol for Heart Failure
- ClinicalTrials.gov ID
- NCT01586156
- Acronym / sponsor ID
- PAHTCH / 11-1198
- Conditions
- Pulmonary Hypertension
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Dec 2012
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 26 Apr 2012 (estimated)
- Results
- Posted 30 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature leading to elevated pulmonary pressure and right ventricular (RV) dysfunction with heart failure. Measures of RV function are better predictors of mortality and long term outcomes than pulmonary vascular resistance. The interaction between RV function and the pulmonary circulation is not fully understood, but increased after load appears insufficient to explain right heart failure. Yet, all approved PAH therapies target vasodilation of the pulmonary vasculature to lower pressures
Detailed description
Pulmonary arterial hypertension (PAH) is a serious condition characterized by endothelial dysfunction leading to pulmonary vascular constriction, smooth muscle and endothelial proliferation, and progressive right-sided heart failure. The severity of pulmonary hypertension is mostly determined by the response of the right ventricle (RV) to the increased afterload or pulmonary pressures, and RV failure is the leading cause of death in PAH. Most accepted therapies for PAH have been aimed at vasodilation of the pulmonary vasculature, and there has been little thought that PAH patients would benefit from traditional left heart failure treatments. A cornerstone therapy in left heart failure is £]-adrenergic receptor blockade because of its ability to reverse cardiac remodeling and improve clinical outcomes, despite decades of concern regarding its propensity to exacerbate heart failure. It has been reported to reduce mortality by about 30% in patients, and while the precise mechanisms that contribute to its beneficial effects remain to be elucidated, there is evidence that patients with underlying contractile reserve (i.e., via recruitment of viable myocardium with £]-adrenergic receptor stimulation) may experience greater recovery of their cardiac function. In a study using rats with pulmonary hypertension treated with £] blocker, RV function improved, and maladaptive myocardial remodeling was prevented.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Open Label Carvedilol | Active comparator | Drug: CarvedilolEligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight to the CRU (Clinical Research Unit) for the first-dose challenge of carvedilol. Subjects will take the medication for one week and at the end of one week, eligible subjects will be randomized to one of two groups (blinded). Group 1 will receive 3.125mg twice daily for six months.Group 2 will receive carvedilol in a dose escalation scheme. They will be given 3.125mg tablets to take twice daily for one week, followed by 6.25 mg twice daily for one week, followed by 12.5mg twice daily for one week with the option to increase to the max dose of 25mg twice daily for the remainder of the study. |
| Placebo Arm | Placebo comparator | Drug: placeboEligible subjects will receive open label carvedilol therapy at a dose 3.125 mg twice daily for one week. Subjects will be admitted overnight for the first-dose challenge of carvedilol. After one week run in phase, subjects will be placed on placebo. Subjects and Investigators will be blinded to the group assignment for the duration of the study. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women age 18 or older not greater than age 65 years
- Diagnosis of pulmonary arterial hypertension class 1, 3, 4, 5 (Dana Point 2008)
- NYHA (New York Health Association)/WHO (World Health Organization) Class I-III
- PAH medications must have been initiated according to the latest consensus statement recommendations and remained stable for the last 30 days
- Women of child-bearing age must use a double-barrier local contraception till completion of the study
Key exclusion criteria (13 listed)
- Participation in any other treatment studies during enrollment
- Significant illness in the past 30 days requiring hospitalization
- Hepatic insufficiency (transaminase levels > 4 fold the upper limit of normal or bilirubin > 2 fold the upper limit of normal),
- History of HIV, Hepatitis B or C
- Serum creatinine > 2.8 mg/dl
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 |
|---|---|---|
| CarvedilolAlso: low fixed dose, escalating doseGroup 1 will receive 3.125mg carvedilol twice daily for six months.Group 2 will receive carvedilol in a dose escalation scheme. | Drug | Open Label Carvedilol |
| placeboPlacebo will be taken twice daily for 6 months | Drug | Placebo Arm |
Primary outcome
Cardiac Glucose Uptake in FDG-PET (Fluorodeoxyglucose-Positron Emission Tomography)
Time frame: 6 months
We hypothesize that use of carvedilol in patients with PAH (Pulmonary Arterial Hypertension) will decrease the cardiac glucose utilization, and this will be measurable as a drop in fasting FDG-PET standardized uptake values of the heart at 6 months as compared to baseline
2 secondary outcomes
Urinary cAMP (Cyclic Adenosine Monophosphate)/Creatinine
Time frame: 6 months
Beta-Adrenergic Receptor (Alprenolol Binding Assay)
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28814664Farha S, Saygin D, Park MM, Cheong HI, Asosingh K, Comhair SA, Stephens OR, Roach EC, Sharp J, Highland KB, DiFilippo FP, Neumann DR, Tang WHW, Erzurum SC. Pulmonary arterial hypertension treatment with carvedilol for heart failure: a randomized controlled trial. JCI Insight. 2017 Aug 17;2(16):e95240. doi: 10.1172/jci.insight.95240. eCollection 2017 Aug 17.
- Results publication: PubMed 28597761Saygin D, Highland KB, Farha S, Park M, Sharp J, Roach EC, Tang WHW, Thomas JD, Erzurum SC, Neumann DR, DiFilippo FP. Metabolic and Functional Evaluation of the Heart and Lungs in Pulmonary Hypertension by Gated 2-[18F]-Fluoro-2-deoxy-D-glucose Positron Emission Tomography. Pulm Circ. 2017 Apr-Jun;7(2):428-438. doi: 10.1177/2045893217701917. Epub 2017 Mar 10.
- Results publication: PubMed 26140151Park JH, Park MM, Farha S, Sharp J, Lundgrin E, Comhair S, Tang WH, Erzurum SC, Thomas JD. Impaired Global Right Ventricular Longitudinal Strain Predicts Long-Term Adverse Outcomes in Patients with Pulmonary Arterial Hypertension. J Cardiovasc Ultrasound. 2015 Jun;23(2):91-9. doi: 10.4250/jcu.2015.23.2.91. Epub 2015 Jun 26.
- Derived from this study: PubMed 31242023Stephens OR, Weiss K, Frimel M, Rose JA, Sun Y, Asosingh K, Farha S, Highland KB, Prasad SVN, Erzurum SC. Interdependence of hypoxia and beta-adrenergic receptor signaling in pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2019 Sep 1;317(3):L369-L380. doi: 10.1152/ajplung.00015.2019. Epub 2019 Jun 26.
- Derived from this study: PubMed 30619887Cheong HI, Farha S, Park MM, Thomas JD, Saygin D, Comhair SAA, Sharp J, Highland KB, Tang WHW, Erzurum SC. Endothelial Phenotype Evoked by Low Dose Carvedilol in Pulmonary Hypertension. Front Cardiovasc Med. 2018 Dec 12;5:180. doi: 10.3389/fcvm.2018.00180. eCollection 2018.
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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.
Serpil Erzurum, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Carvedilol in people with Pulmonary Hypertension, run by The Cleveland Clinic 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 6 inclusion and 13 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: finished, as of the sponsor's last update on 5 Dec 2018. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Cardiac Glucose Uptake in FDG-PET (Fluorodeoxyglucose-Positron Emission Tomography) (time frame: 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 NCT01586156, which also lists 5 linked publications.
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 5 Dec 2018.