Epoprostenol for Injection (EFI/ACT-385781A) - Pulmonary Arterial Hypertension (EPITOME-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT01431716
First received: September 7, 2011
Last updated: January 2, 2015
Last verified: January 2015
  Purpose

This study is investigating the effect of switching from Flolan® to Epoprostenol for Injection (EFI/ACT-385781A) in pulmonary arterial hypertension patients currently treated with Flolan®. For this purpose patients being treated for at least 12 months with Flolan® will be switched from Flolan® to EFI/ACT-385781A and followed-up for 90 days. During these 90 days safety and tolerability of EFI/ACT-385781A will closely be monitored in all treated patients. This 90 follow-up will provide clinical evidence on the safety, tolerability, efficacy and treatment satisfaction of switching from Flolan® to EFI/ACT-385781A in patients with pulmonary arterial hypertension.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: EFI/ACT-385781A
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Single-arm, Open-label, Phase 3b Study to Assess the Effects of Switching From Flolan® to EFI/ACT-385781A in Patients With Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Change in Pulmonary Vascular Resistance From Baseline to End of Treatment (EOT). [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    Right heart catheterization was performed for cardiac hemodynamic assessment at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.

  • Change in Total Pulmonary Resistance From Baseline to End of Treatment (EOT). [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    Right heart catheterization was performed for cardiac hemodynamic assessment at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.

  • Change in Mean Pulmonary Arterial Pressure From Baseline to End of Treatment (EOT). [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    Right heart catheterization was performed for cardiac hemodynamic assessment at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.

  • Change in Mean Right Atrial Pressure From Baseline to End of Treatment (EOT). [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    Right heart catheterization was performed for cardiac hemodynamic assessment at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.

  • Change in Pulmonary Capillary Wedge Pressure From Baseline to End of Treatment (EOT). [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    Right heart catheterization was performed for cardiac hemodynamic assessment at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.

  • Change in Mean Cardiac Index From Baseline to End of Treatment (EOT). [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    Right heart catheterization was performed for cardiac hemodynamic assessment at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.


Other Outcome Measures:
  • Change in 6-minute Walk Distance (6MWD) From Baseline to EOT. [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    The 6MWD was assessed at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT. The 6-minute walk test is a non-encouraged test that measures the distance walked for the duration of 6 min.

  • Change in Borg Dyspnea Score From Baseline to EOT. [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    The Borg dyspnea score was assessed at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT. The Borg scale is a category-ratio scale, commonly used to evaluate the effects of exercise on dyspnea. The original and modified scales have ratio properties ranging from 0 = nothing at all to 10 = very, very severe, with descriptors from 0 to 10. Descriptors have been modified by others so that 10 has been labelled "extremely severe," or "the worst possible dyspnea imaginable."

  • Number of Participants With Improved, No Change, or Worsening of New York Heart Association Functional Class (NYHA FC) From Baseline to EOT. [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    NYHA FC was assessed at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT. Disease severity was assessed by NYHA classification of pulmonary arterial hypertension criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.

  • Change in N-terminal Pro-B-type Natriuretic Peptide (NT proBNP) From Baseline to EOT. [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    Blood sampling for NT proBNP was performed at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.

  • Change in Effectiveness Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT. [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    Patients were required to complete the TSQM-9 questionnaire at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT. The TSQM-9 is a validated instrument to assess patients' satisfaction with medication, including a three question effectiveness scale. The TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain.

  • Change in Convenience Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT. [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    Patients were required to complete the TSQM-9 questionnaire at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT. The TSQM-9 is a validated instrument to assess patients' satisfaction with medication, including a three question convenience scale. The TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain.

  • Change in Global Satisfaction Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT. [ Time Frame: Approximately 3 months ] [ Designated as safety issue: No ]
    Patients were required to complete the TSQM-9 questionnaire at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT. The TSQM-9 is a validated instrument to assess patients' satisfaction with medication, including a three question global satisfaction scale. The TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain.

  • Number of Participants With Adverse Events Leading to Discontinuation of Study Drug From Baseline to EOT. [ Time Frame: Approximately 3 months ] [ Designated as safety issue: Yes ]
    Adverse events that led to discontinuation of study drug from the start of study treatment until the end of study treatment were recorded.


Enrollment: 42
Study Start Date: March 2011
Study Completion Date: July 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EFI/ACT-385781A
EFI/ACT-385781 administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump
Drug: EFI/ACT-385781A
Other Names:
  • ACT-385781A
  • Epoprostenol for injection (EFI)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female aged 18 years and above
  2. Patients with the following types of pulmonary arterial hypertension (PAH) belonging to WHO Group I: Idiopathic (IPAH), Heritable (HPAH), Associated (APAH) with Connective tissue diseases or Drugs and toxins
  3. Patients treated with Flolan® for at least 12 months and on a stable dose for at least 3 months prior to enrollment
  4. Patients who are currently treated with concomitant PAH therapy listed below must have been treated for at least 90 days and on a stable dose for 30 days prior to enrollment: Bosentan, Ambrisentan, Sitaxsentan, Sildenafil, Tadalafil
  5. Women of childbearing potential must use a reliable method of contraception
  6. Signed informed consent prior to initiation of any study mandated procedure

Exclusion Criteria:

  1. Patients with respiratory and/or cardiovascular distress in need of emergency care
  2. Known or suspicion of pulmonary veno-occlusive disease (PVOD)
  3. Current use of IV inotropic agents
  4. Current use of any prostacyclin or prostacyclin analog other than Flolan®
  5. Tachycardia with heart rate > 120 beats/min at rest
  6. PAH related to any condition other than those specified in the inclusion criteria
  7. Known hypersensitivity to the formulations EFI/ACT-385781A or any of its excipients, and Flolan® or any of its excipients
  8. Cerebrovascular events (e.g., transient ischemic attack or stroke) within 6 months of screening
  9. History of myocardial infarction
  10. History of left-sided heart disease, including any of the following:

    • hemodynamically significant aortic or mitral valve disease
    • restrictive or congestive cardiomyopathy
    • left ventricular ejection fraction < 40% by multigated radionucleotide angiogram (MUGA), angiography, or echocardiography
    • unstable angina pectoris
    • life-threatening cardiac arrhythmias
  11. Chronic bleeding disorders
  12. Central venous line infection within 90 days prior to screening and/or a history of recurring line infections
  13. Women who are pregnant or breast-feeding
  14. Participation in another clinical trial, except observational, or receipt of an investigational product within 30 days prior to randomization
  15. Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease
  16. Known concomitant life-threatening disease other than PAH with a life expectancy < 12 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01431716

Locations
Belgium
UZ Gasthuisberg
Leuven, Belgium, 3000
Canada, Ontario
University Health Network, Toronto TGH - 10 EN - 220
Toronto, Ontario, Canada, M5G 2N2
Canada, Quebec
Sir Mortimer B Davis Jewish General Hospital
Montreal, Quebec, Canada, H3T 1 E2
France
Centre Hospitalier Universitaire
Caen, France, 14033
Hôpital Antoine Béclère
Clamart Cedex, France, 92141
Italy
Orsola Malpighi
Bologna, Italy, 40138
Netherlands
VU Medisch Centrum (VUMC)
Amsterdam, Netherlands, 1081 HV
Spain
Hospital Vall d'Hebron
Barcelona, Spain, 8035
Sponsors and Collaborators
Actelion
  More Information

No publications provided

Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01431716     History of Changes
Other Study ID Numbers: AC-066A301
Study First Received: September 7, 2011
Results First Received: January 2, 2015
Last Updated: January 2, 2015
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Ethics Review Committee
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Committee for the Protection of Personnes
Italy: Ethics Committee
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on March 25, 2015