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

Primary Purpose

Pulmonary Arterial Hypertension

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
EFI/ACT-385781A
Sponsored by
Actelion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UZ Gasthuisberg
  • University Health Network, Toronto TGH - 10 EN - 220
  • Sir Mortimer B Davis Jewish General Hospital
  • Centre Hospitalier Universitaire
  • Hôpital Antoine Béclère
  • Orsola Malpighi
  • VU Medisch Centrum (VUMC)
  • Hospital Vall d'Hebron

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

EFI/ACT-385781A

Arm Description

EFI/ACT-385781 administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump

Outcomes

Primary Outcome Measures

Change in Pulmonary Vascular Resistance From Baseline to End of Treatment (EOT).
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).
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).
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).
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).
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).
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.

Secondary Outcome Measures

Full Information

First Posted
September 7, 2011
Last Updated
January 2, 2015
Sponsor
Actelion
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1. Study Identification

Unique Protocol Identification Number
NCT01431716
Brief Title
Epoprostenol for Injection (EFI/ACT-385781A) - Pulmonary Arterial Hypertension
Acronym
EPITOME-2
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EFI/ACT-385781A
Arm Type
Experimental
Arm Description
EFI/ACT-385781 administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump
Intervention Type
Drug
Intervention Name(s)
EFI/ACT-385781A
Other Intervention Name(s)
ACT-385781A, Epoprostenol for injection (EFI)
Primary Outcome Measure Information:
Title
Change in Pulmonary Vascular Resistance From Baseline to End of Treatment (EOT).
Description
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.
Time Frame
Approximately 3 months
Title
Change in Total Pulmonary Resistance From Baseline to End of Treatment (EOT).
Description
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.
Time Frame
Approximately 3 months
Title
Change in Mean Pulmonary Arterial Pressure From Baseline to End of Treatment (EOT).
Description
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.
Time Frame
Approximately 3 months
Title
Change in Mean Right Atrial Pressure From Baseline to End of Treatment (EOT).
Description
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.
Time Frame
Approximately 3 months
Title
Change in Pulmonary Capillary Wedge Pressure From Baseline to End of Treatment (EOT).
Description
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.
Time Frame
Approximately 3 months
Title
Change in Mean Cardiac Index From Baseline to End of Treatment (EOT).
Description
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.
Time Frame
Approximately 3 months
Other Pre-specified Outcome Measures:
Title
Change in 6-minute Walk Distance (6MWD) From Baseline to EOT.
Description
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.
Time Frame
Approximately 3 months
Title
Change in Borg Dyspnea Score From Baseline to EOT.
Description
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."
Time Frame
Approximately 3 months
Title
Number of Participants With Improved, No Change, or Worsening of New York Heart Association Functional Class (NYHA FC) From Baseline to EOT.
Description
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.
Time Frame
Approximately 3 months
Title
Change in N-terminal Pro-B-type Natriuretic Peptide (NT proBNP) From Baseline to EOT.
Description
Blood sampling for NT proBNP was performed at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.
Time Frame
Approximately 3 months
Title
Change in Effectiveness Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT.
Description
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.
Time Frame
Approximately 3 months
Title
Change in Convenience Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT.
Description
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.
Time Frame
Approximately 3 months
Title
Change in Global Satisfaction Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT.
Description
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.
Time Frame
Approximately 3 months
Title
Number of Participants With Adverse Events Leading to Discontinuation of Study Drug From Baseline to EOT.
Description
Adverse events that led to discontinuation of study drug from the start of study treatment until the end of study treatment were recorded.
Time Frame
Approximately 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female aged 18 years and above 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 Patients treated with Flolan® for at least 12 months and on a stable dose for at least 3 months prior to enrollment 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 Women of childbearing potential must use a reliable method of contraception Signed informed consent prior to initiation of any study mandated procedure Exclusion Criteria: Patients with respiratory and/or cardiovascular distress in need of emergency care Known or suspicion of pulmonary veno-occlusive disease (PVOD) Current use of IV inotropic agents Current use of any prostacyclin or prostacyclin analog other than Flolan® Tachycardia with heart rate > 120 beats/min at rest PAH related to any condition other than those specified in the inclusion criteria Known hypersensitivity to the formulations EFI/ACT-385781A or any of its excipients, and Flolan® or any of its excipients Cerebrovascular events (e.g., transient ischemic attack or stroke) within 6 months of screening History of myocardial infarction 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 Chronic bleeding disorders Central venous line infection within 90 days prior to screening and/or a history of recurring line infections Women who are pregnant or breast-feeding Participation in another clinical trial, except observational, or receipt of an investigational product within 30 days prior to randomization 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 Known concomitant life-threatening disease other than PAH with a life expectancy < 12 months
Facility Information:
Facility Name
UZ Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
University Health Network, Toronto TGH - 10 EN - 220
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada
Facility Name
Sir Mortimer B Davis Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1 E2
Country
Canada
Facility Name
Centre Hospitalier Universitaire
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
Hôpital Antoine Béclère
City
Clamart Cedex
ZIP/Postal Code
92141
Country
France
Facility Name
Orsola Malpighi
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
VU Medisch Centrum (VUMC)
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
8035
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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

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