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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01431716

Acronym

EPITOME-2

Enrollment

Registered

2011-09-12

Start date

2011-03-31

Completion date

2012-07-31

Last updated

2015-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary Arterial Hypertension

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.

Interventions

DRUGEFI/ACT-385781A

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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

Design outcomes

Primary

Measure	Time frame	Description
Change in Pulmonary Vascular Resistance From Baseline to End of Treatment (EOT).	Approximately 3 months	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).	Approximately 3 months	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).	Approximately 3 months	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).	Approximately 3 months	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).	Approximately 3 months	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).	Approximately 3 months	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

Measure	Time frame	Description
Change in Global Satisfaction Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT.	Approximately 3 months	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.
Change in 6-minute Walk Distance (6MWD) From Baseline to EOT.	Approximately 3 months	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.
Number of Participants With Adverse Events Leading to Discontinuation of Study Drug From Baseline to EOT.	Approximately 3 months	Adverse events that led to discontinuation of study drug from the start of study treatment until the end of study treatment were recorded.
Change in Borg Dyspnea Score From Baseline to EOT.	Approximately 3 months	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.	Approximately 3 months	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.	Approximately 3 months	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.	Approximately 3 months	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.	Approximately 3 months	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.

Countries

Belgium, Canada, France, Italy, Netherlands, Spain

Participant flow

Recruitment details

Patients were enrolled at eight centers in the European Union and Canada. First patient, first visit was 15 March 2011 and last patient, last visit was 2 February 2012.

Pre-assignment details

Patients must have been treated with Flolan for at least 12 months and on a stable dose for at least 3 months prior to enrollment. There was a screening period of up to 14 days.

Participants by arm

Arm	Count
EFI/ACT-385781A EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.	41
Total	41

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal of consent	1

Baseline characteristics

Characteristic	EFI/ACT-385781A
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	3 Participants
Age, Categorical Between 18 and 65 years	38 Participants
Age, Continuous	44.8 years STANDARD_DEVIATION 13.9
Race/Ethnicity, Customized Asian	1 participants
Race/Ethnicity, Customized Black	2 participants
Race/Ethnicity, Customized Not Collected	20 participants
Race/Ethnicity, Customized White/Caucasian	18 participants
Region of Enrollment Belgium	5 participants
Region of Enrollment Canada	8 participants
Region of Enrollment France	20 participants
Region of Enrollment Italy	2 participants
Region of Enrollment Netherlands	4 participants
Region of Enrollment Spain	2 participants
Sex: Female, Male Female	30 Participants
Sex: Female, Male Male	11 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	31 / 41
serious Total, serious adverse events	7 / 41

Outcome results

Primary

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.