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Pulmonary HypertensionPhase 2SPHERE-HFNCT02775539

Beta3 Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure

A Phase 2 study testing Mirabegron in people with Pulmonary Hypertension and Mirabegron, run by Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this study is to evaluate the efficacy and safety of mirabegron (a B3 adrenergic receptor agonist) in patients with pulmonary hypertension secondary to heart failure by conducting a randomized multicenter phase II placebo-controlled clinical trial. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pulmonary Hypertension, Mirabegron, Heart Failure
What is being tested?
Mirabegron
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
80 participants
Where
No sites listed yet
Study dates
Jun 2016to Jun 2019
Phase
Phase 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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written inform consent;
  • >18 years-old;
  • HF with reduced or preserved ejection fraction, according to the definition of the European Society of Cardiology guidelines.
  • Severe PH and/or combined postcapillary and precapillary PH (also knows as reactive or out-of-proportion PH) determined by RHC showing the following:
  • Pulmonary arterial wedge pressure or end-diastolic left ventricular pressures ≥15 mmHg;
  • Mean PAP≥25, and:
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  • PVR≥3 UW and/or diastolic gradient≥7 mmHg or
  • Transpulmonary gradient≥12.
  • NYHA functional class II-IV;
  • On optimized evidence-based pharmacological treatment;
  • Stable clinical condition defined as no changes in therapeutic regimen or hospitalization in the 30 days preceding recruitment and no current plan for changing therapy.

Who cannot join

  • Non-coronary cardiac surgery or non-coronary percutaneous procedure within the 12 months preceding recruitment or programmed;
  • Myocardial infarction or coronary revascularization during the last 3 months,
  • Myocardial resynchronization therapy initiated during the last 6 months;
  • Sinus tachycardia or atrial fibrillation with uncontrolled heart rate (>100 bpm);
  • Uncontrolled hypertension (PAS>180 or PAD>110 mmHg) or symptomatic hypotension (PAS<90 mmHg).
  • Infiltrative myocardial disease.
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  • Expected survival <1 year due to a disease other than PH;
  • Severe renal failure (GFR <30 mL/min/1.73 m2 or haemodialysis);
  • Severe hepatic impairment (serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3x the upper limit of normality at screening;
  • cQT interval on the ECG >430 ms in male or >450 ms in female;
  • Concomitant use of specific pulmonary vasodilator therapy (i.e. endothelin receptor antagonists, phosphodiesterase -5 inhibitors, guanylate cyclase stimulators).
  • Concomitant use of digoxin, flecainide, propafenone, dabigatran, tricycle antidepressants, or another strong inhibitors of CYP2D6 (with the exception of betablockers).
  • Significant obstructive lung disease (FEV1/FVC<0.7 associated with FEV1<50% of predicted value).
  • Significant restrictive lung disease (TLC<60%).
  • Participation in another clinical trial.
  • Female with childbearing potential.
  • Known hypersensitivity to mirabegron or to any of its excipients.

Trial locations and contacts

No sites are listed yet.

Ana García-Álvarez, MD, PhD contact

003491 4531200 ext. 1507

anagarci@clinic.ub.es

Borja Ibañez, MD, PhD contact

003491 4531200 ext. 1507

bibanez@cnic.es

About this study

Official title: Beta3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure

The purpose of this study is to evaluate the efficacy and safety of mirabegron (a B3 adrenergic receptor agonist) in patients with pulmonary hypertension secondary to heart failure by conducting a randomized multicenter phase II placebo-controlled clinical trial.

Read the detailed description

Pulmonary hypertension (PH) affects 60-80% of patients with chronic heart failure (HF) and has a critical impact on prognosis. Currently, there is no specific treatment approved for this indication. Experimental research, performed by members of the consortium, demonstrates that treatment with B3 adrenergic receptor agonists produces a beneficial effect on pulmonary hemodynamics, right ventricular (RV) remodeling and pulmonary vascular proliferation in a translational pig model of postcapillary PH. Mirabegron, an oral B3AR agonist, is currently approved for a different medical condition (overactive bladder syndrome) with a good safety profile. Our main objective is to evaluate the efficacy and safety of mirabegron in patients with PH secondary to HF.

The objective will be evaluated by conducting a phase-2 randomized placebo-controlled clinical trial in patients with PH associated to HF. Patients will be randomized 1:1 to mirabegron or placebo, and dose will be titrated till 200 mg/day. Patients will be evaluated with quality of life questionnaire, blood analysis, ECG, echocardiography, 6-minute walking test, right heart catheterization (RHC) and cardiac magnetic resonance (CMR) at baseline and after 16 weeks of treatment.

Being tested
Mirabegron, Placebo
Keywords
Pulmonary hypertension, Mirabegron, Heart failure, B3 adrenergic
Medical subject headings
Hypertension, Pulmonary, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MirabegronDrug

    Patients will receive 50 to 200 mg of mirabegron once a day during 16 weeks. Dose will be titrated during the first 8 weeks.

  • PlaceboDrug

Study groups in NCT02775539
Study groupRoleWhat they receive
MirabegronActive comparatorOral mirabegron, starting with 50 mg once a day and titrated till a maximum of 200 mg once a day.
Receives: Drug: Mirabegron
PlaceboPlacebo comparatorOral placebo, similarly titrated to ensure blindness.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in pulmonary vascular resistance (PVR) from baseline to week 16 assessed by right heart catheterization (RHC).

    Measured: 16 weeks

Secondary outcomes (14)

  1. Change from baseline in 6-minute walking distance

    Measured: 16 weeks

  2. Change from baseline in NYHA functional class

    Measured: 16 weeks

  3. Change from baseline in quality of life

    Measured: 16 weeks

  4. Change from baseline in dyspnea Borg score

    Measured: 16 weeks

  5. Change from baseline in mean PAP as assessed by RHC

    Measured: 16 weeks

  6. Change from baseline in cardiac index (CI) as assessed by RHC and cardiac magnetic resonance (CMR)

    Measured: 16 weeks

  7. Change from baseline in RV ejection fraction as assessed by CMR

    Measured: 16 weeks

  8. Change from baseline in BNP/NT-proBNP

    Measured: 16 weeks

  9. Hospital admissions due to worsening cardiopulmonary status

    Measured: 16 weeks

  10. Mortality

    Measured: 16 weeks

  11. Urgent heart transplantation

    Measured: 16 weeks

  12. New onset arrhythmia

    Measured: 16 weeks

  13. Need for initiation of intravenous therapy due to worsening HF

    Measured: 16 weeks

  14. Adverse drug effects

    Measured: 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2016 (estimated)
  2. Study startJun 2016
  3. Primary completionJan 2017 (estimated)
  4. Study completionJun 2019 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02775539
Sponsor's protocol ID
SPHERE-HF
Acronym
SPHERE-HF
Status last verified
May 2016
First submitted
14 May 2016
Last updated
17 May 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Garcia-Lunar I, Blanco I, Fernandez-Friera L, Prat-Gonzalez S, Jorda P, Sanchez J, Pereda D, Pujadas S, Rivas M, Sole-Gonzalez E, Vazquez J, Blazquez Z, Garcia-Picart J, Caravaca P, Escalera N, Garcia-Pavia P, Delgado J, Segovia-Cubero J, Fuster V, Roig E, Barbera JA, Ibanez B, Garcia-Alvarez A. Design of the beta3-Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure Trial. JACC Basic Transl Sci. 2020 Mar 11;5(4):317-327. doi: 10.1016/j.jacbts.2020.01.009. eCollection 2020 Apr.

    PubMed 32368692

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Mirabegron in people with Pulmonary Hypertension and Mirabegron, run by Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III.

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 11 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 17 May 2016. Status can change between updates, so confirm with the study contact before making plans.

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.

What does this phase mean?

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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Ana García-Álvarez, MD, PhD (003491 4531200 ext. 1507, anagarci@clinic.ub.es), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in pulmonary vascular resistance (PVR) from baseline to week 16 assessed by right heart catheterization (RHC). (time frame: 16 weeks). 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 NCT02775539, 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 17 May 2016.

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