Efficacy and Safety of Upfront Combination of ΒΟsentan and ΤΑdalafil in Pulmonary Arterial Hypertension (BOTA-PAH)
24 de enero de 2018 actualizado por: Elpen Pharmaceutical Co. Inc.
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.
Descripción general del estudio
Estado
Retirado
Condiciones
Descripción detallada
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
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.
Is safe as assessed by
- Liver function markers such as serum SGOT and SGPT levels
- Hemoglobin levels
Tipo de estudio
De observación
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 75 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
N/A
Géneros elegibles para el estudio
Todos
Método de muestreo
Muestra no probabilística
Población de estudio
Newly diagnosed patients with PAH
Descripción
Inclusion Criteria:
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.
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
Exclusion Criteria:
- 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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Month 6
Periodo de tiempo: 6 months
|
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.
|
6 months
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Number of Participants With First Adjudicated Clinical Failure (CF) Event
Periodo de tiempo: 6 months
|
Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Clinical Response
|
6 months
|
|
Time to first clinical worsening (TTCW) event
Periodo de tiempo: 6 months
|
TTCW defined as the number of days between first dose of study drug and the occurrence of a predefined clinical worsening event.
|
6 months
|
|
Percentage of Participants With a Satisfactory Clinical Response at Month 6
Periodo de tiempo: 6 months
|
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;
|
6 months
|
|
Change From Baseline in the World Health Organization Functional Class at month 6
Periodo de tiempo: 6 months
|
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.
|
6 months
|
|
Change From Baseline in the 6 Minute Walk Distance (6MWD) Test at month 6
Periodo de tiempo: 6 months
|
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. |
6 months
|
|
Change From Baseline in Borg Dyspnea Index at month 6
Periodo de tiempo: 6 months
|
Borg Dyspnea Index (BDI) indicates the degree of breathlessness after completion of the 6 minute walk test.
|
6 months
|
|
Quality of Life
Periodo de tiempo: 6 moths
|
Change in emPHasis-10 questionnaire score
|
6 moths
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
- 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.
- 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.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Anticipado)
1 de diciembre de 2017
Finalización primaria (Anticipado)
1 de diciembre de 2019
Finalización del estudio (Anticipado)
1 de diciembre de 2019
Fechas de registro del estudio
Enviado por primera vez
28 de abril de 2017
Primero enviado que cumplió con los criterios de control de calidad
2 de mayo de 2017
Publicado por primera vez (Actual)
3 de mayo de 2017
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
26 de enero de 2018
Última actualización enviada que cumplió con los criterios de control de calidad
24 de enero de 2018
Última verificación
1 de agosto de 2017
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 2017-BSN-EL-73
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
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