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Pulmonary HypertensionBOTA-PAHNCT03139084

Efficacy and Safety of Upfront Combination of ΒΟsentan and ΤΑdalafil in Pulmonary Arterial Hypertension

An observational study of Pulmonary Hypertension, run by Elpen Pharmaceutical Co. Inc..

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The development of disease-targeted drugs for the treatment of pulmonary arterial hypertension (PAH) has significantly improved within the last years. Combining drug products with different mechanisms of action such as Endothelin-Receptor-Antagonists (ERAs) and Phosphodiesterase-Type-5-inhibitors (PDE-5-Inhibitors)… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Pulmonary Hypertension
How many people
0 participants
Where
No sites listed yet
Study dates
1 Dec 2017to 1 Dec 2019
Phase
Observational
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 75 years
  • All sexes
  • Adult, Older adult

Study population: Newly diagnosed patients with PAH

Who may be able to join

  • Male or females between 18 to 75 years of age at inclusion
  • Diagnosis of PAH due to the following:
  • Idiopathic Primary Pulmonary Arterial Hypertension (IPAH)
  • Hereditary PAH
  • PAH secondary to connective tissue disease
  • PAH diagnosis confirmed by right heart catheterization performed within 3 months prior to study enrolment Subjects must weigh at least 40 kg at inclusion Subject must have a current diagnosis of being in World Health Organisation (WHO) Functional Class II or III.
Show all 11Show fewer
  • Treatment PAH naïve subjects PAH documented by
  • mPAP ≥25mmHg,
  • pulmonary capillary wedge pressure (PCWP) or
  • left ventricular end-diastolic pressure (LVEDP) ≤15mmHg and
  • PVR ≥3 Wood Units. Subject must walk a distance of ≥125m and ≤500m at the screening visit

Who cannot join

  • History of pulmonary embolism
  • No prior treatment with PDE-5 inhibitors
  • History of chronic lung disease / restrictive lung disease (eg, chronic obstructive pulmonary disease (COPD) or scleroderma) with impairment of lung function
  • Current treatment with nitrates or nitric oxide
  • Significant (ie, >2+) valvular disease other than tricuspid regurgitation or pulmonary regurgitation
  • History of cardiac arrest, respiratory arrest, hemodynamic collapse, CPR, ventricular tachycardia, ventricular fibrillation, or uncontrolled atrial fibrillation

About this study

Official title: An Observational, Non-interventional, Multicenter Study to Evaluate the Efficacy and Safety of Upfront Combination of Bosentan and Tadalafil in Pulmonary Arterial Hypertension in Greek Patients

The development of disease-targeted drugs for the treatment of pulmonary arterial hypertension (PAH) has significantly improved within the last years. Combining drug products with different mechanisms of action such as Endothelin-Receptor-Antagonists (ERAs) and Phosphodiesterase-Type-5-inhibitors (PDE-5-Inhibitors) has become increasingly important for the treatment of PAH. Recently, the results of the AMBITION study reported that an upfront combination treatment of ambrisentan and tadalafil immediately after diagnosis leads to a delayed disease progression. On the other hand, the sequential combination of bosentan and sildenafil did not show a similar positive clinical effect and this was attributed to a negative clinically relevant pharmacodynamic drug-drug interaction. Although, recent guidelines have extrapolated that initial upfront combination treatment follows a class effect in terms of efficacy and safety, there is an imperative need to support this notion with other combinations of ERAs and PDE-5-Inhibitors.

Read the detailed description

The primary objective of BOTA study is to compare the change in clinical and hemodynamic measures of PAH after the initiation of first line combination therapy with bosentan and tadalafil in adult patients with PAH. The safety and tolerability of first line combination therapy will also be evaluated.

In patients with PAH initial upfront combination treatment with bosentan and tadalafil

  1. Improves
  • Exercise capacity as expressed by distance walked in six minute walk test and WHO functional class
  • Hemodynamics in terms of pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP) reduction and cardiac index (CI) elevation
  • Quality of life
  • NTproBNP serum levels
  • Echocardiographic prognostic parameters such as right atrial area and presence of pericardial effusion.
  1. Is safe as assessed by
  • Liver function markers such as serum SGOT and SGPT levels
  • Hemoglobin levels
Medical subject headings
Hypertension, Pulmonary

What is being measured

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

  1. Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Month 6

    N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) is a surrogate marker of heart failure. The geometric mean ratio will be calculated as the ratio between the month 6 value and the Baseline value and presented as percent change = 100 * (geometric mean ratio - 1). The Baseline value is the last value prior to administration of study drug; this may be prior to or on the day of study drug initiation.

    Measured: 6 months

Secondary outcomes (7)

  1. Number of Participants With First Adjudicated Clinical Failure (CF) Event

    Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Clinical Response

    Measured: 6 months

  2. Time to first clinical worsening (TTCW) event

    TTCW defined as the number of days between first dose of study drug and the occurrence of a predefined clinical worsening event.

    Measured: 6 months

  3. Percentage of Participants With a Satisfactory Clinical Response at Month 6

    A satisfactory clinical response at month 6 is defined as a participant who meets all of the following criteria: 10% improvement in 6MWD compared with Baseline;

    Measured: 6 months

  4. Change From Baseline in the World Health Organization Functional Class at month 6

    Change From Baseline in the World Health Organization Functional Class Time Frame: Baseline and Month 6 The WHO Functional Class (FC) indicates the severity of PAH and is an adaptation of the New York Heart Association classification.

    Measured: 6 months

  5. Change From Baseline in the 6 Minute Walk Distance (6MWD) Test at month 6

    Change From Baseline in the 6 Minute Walk Distance (6MWD) Test at month 6

    MWD is the distance a participant can walk in 6 minutes. The 6-minute walk distance (6MWD) test measures the distance that a participant can walk in a period of 6 minutes.

    Measured: 6 months

  6. Change From Baseline in Borg Dyspnea Index at month 6

    Borg Dyspnea Index (BDI) indicates the degree of breathlessness after completion of the 6 minute walk test.

    Measured: 6 months

  7. Quality of Life

    Change in emPHasis-10 questionnaire score

    Measured: 6 moths

Timeline

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

  1. First posted3 May 2017
  2. Study start1 Dec 2017 (estimated)
  3. Primary completion1 Dec 2019 (estimated)
  4. Study completion1 Dec 2019 (estimated)

Why it stopped: Updated results by guidelines and bibliography

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Other
Time perspective
Prospective
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03139084
Sponsor's protocol ID
2017-BSN-EL-73
Acronym
BOTA-PAH
Status last verified
Aug 2017
First submitted
28 Apr 2017
Last updated
26 Jan 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Galie N, Barbera JA, Frost AE, Ghofrani HA, Hoeper MM, McLaughlin VV, Peacock AJ, Simonneau G, Vachiery JL, Grunig E, Oudiz RJ, Vonk-Noordegraaf A, White RJ, Blair C, Gillies H, Miller KL, Harris JH, Langley J, Rubin LJ; AMBITION Investigators. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N Engl J Med. 2015 Aug 27;373(9):834-44. doi: 10.1056/NEJMoa1413687.

    PubMed 26308684

  • McLaughlin V, Channick RN, Ghofrani HA, Lemarie JC, Naeije R, Packer M, Souza R, Tapson VF, Tolson J, Al Hiti H, Meyer G, Hoeper MM. Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension. Eur Respir J. 2015 Aug;46(2):405-13. doi: 10.1183/13993003.02044-2014. Epub 2015 Jun 25.

    PubMed 26113687

  • Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M; ESC Scientific Document Group. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 2016 Jan 1;37(1):67-119. doi: 10.1093/eurheartj/ehv317. Epub 2015 Aug 29. No abstract available.

    PubMed 26320113

Questions about this trial

What is this clinical trial studying?

An observational study of Pulmonary Hypertension, run by Elpen Pharmaceutical Co. Inc..

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 6 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 26 Jan 2018. 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. 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?

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?

Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Month 6 (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 NCT03139084, which also lists 3 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 26 Jan 2018.

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