Trial Outcomes & Findings for Epoprostenol for Injection (EFI/ACT-385781A) - Pulmonary Arterial Hypertension (NCT NCT01431716)

NCT ID: NCT01431716

Last Updated: 2015-01-13

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 42 participants
• Primary outcome timeframe: Approximately 3 months
• Results posted on: 2015-01-13

Participant Flow

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.

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.

Participant milestones

Measure	Epoprostenol for Injection (EFI/ACT-385781A) EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Overall Study STARTED	42
Overall Study COMPLETED	41
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Epoprostenol for Injection (EFI/ACT-385781A) EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Overall Study Withdrawal of consent	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	EFI/ACT-385781A n=41 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Age, Continuous	44.8 years STANDARD_DEVIATION 13.9 • n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	38 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Sex: Female, Male Female	30 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	18 participants n=5 Participants
Race/Ethnicity, Customized Black	2 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants
Race/Ethnicity, Customized Not Collected	20 participants n=5 Participants
Region of Enrollment France	20 participants n=5 Participants
Region of Enrollment Canada	8 participants n=5 Participants
Region of Enrollment Spain	2 participants n=5 Participants
Region of Enrollment Belgium	5 participants n=5 Participants
Region of Enrollment Netherlands	4 participants n=5 Participants
Region of Enrollment Italy	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 3 months

Population: All treated set without imputation for missing values. Data was missing for 5 patients.

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.

Outcome measures

Measure	EFI/ACT-385781A n=36 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Change in Pulmonary Vascular Resistance From Baseline to End of Treatment (EOT). Baseline	595.70 dyn/sec/cm^5 Standard Deviation 237.14
Change in Pulmonary Vascular Resistance From Baseline to End of Treatment (EOT). End of treatment	587.66 dyn/sec/cm^5 Standard Deviation 248.44

PRIMARY outcome

Timeframe: Approximately 3 months

Population: All treated set without imputation for missing values

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.

Outcome measures

Measure	EFI/ACT-385781A n=41 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Change in Total Pulmonary Resistance From Baseline to End of Treatment (EOT). Baseline	752.44 dyn/sec/cm^5 Standard Deviation 260.91
Change in Total Pulmonary Resistance From Baseline to End of Treatment (EOT). End of treatment	757.51 dyn/sec/cm^5 Standard Deviation 296.82

PRIMARY outcome

Timeframe: Approximately 3 months

Population: All treated set without imputation for missing values

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.

Outcome measures

Measure	EFI/ACT-385781A n=41 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Change in Mean Pulmonary Arterial Pressure From Baseline to End of Treatment (EOT). Baseline	51.9 mmHg Standard Deviation 11.5
Change in Mean Pulmonary Arterial Pressure From Baseline to End of Treatment (EOT). End of treatment	51.7 mmHg Standard Deviation 12.8

PRIMARY outcome

Timeframe: Approximately 3 months

Population: All treated set without imputation for missing values

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.

Outcome measures

Measure	EFI/ACT-385781A n=41 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Change in Mean Right Atrial Pressure From Baseline to End of Treatment (EOT). Baseline	7.9 mmHg Standard Deviation 4.6
Change in Mean Right Atrial Pressure From Baseline to End of Treatment (EOT). End of treatment	7.1 mmHg Standard Deviation 4.6

PRIMARY outcome

Timeframe: Approximately 3 months

Population: All treated set without imputation for missing values. Data was missing for 5 patients.

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.

Outcome measures

Measure	EFI/ACT-385781A n=36 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Change in Pulmonary Capillary Wedge Pressure From Baseline to End of Treatment (EOT). Baseline	10.3 mmHg Standard Deviation 3.8
Change in Pulmonary Capillary Wedge Pressure From Baseline to End of Treatment (EOT). End of treatment	10.1 mmHg Standard Deviation 4.3

PRIMARY outcome

Timeframe: Approximately 3 months

Population: All treated set without imputation for missing values

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.

Outcome measures

Measure	EFI/ACT-385781A n=41 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Change in Mean Cardiac Index From Baseline to End of Treatment (EOT). Baseline	3.34 L/min/m^2 Standard Deviation 0.71
Change in Mean Cardiac Index From Baseline to End of Treatment (EOT). End of treatment	3.38 L/min/m^2 Standard Deviation 0.81

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 3 months

Population: All-treated set who had both a baseline and an EOT assessment.

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.

Outcome measures

Measure	EFI/ACT-385781A n=40 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Change in 6-minute Walk Distance (6MWD) From Baseline to EOT. Baseline	498.1 m Standard Deviation 86.0
Change in 6-minute Walk Distance (6MWD) From Baseline to EOT. End of treatment	492.8 m Standard Deviation 81.6

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 3 months

Population: All-treated set who had both a baseline and an EOT assessment.

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."

Outcome measures

Measure	EFI/ACT-385781A n=40 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Change in Borg Dyspnea Score From Baseline to EOT. Baseline	4.0 units on a scale Standard Deviation 2.1
Change in Borg Dyspnea Score From Baseline to EOT. End of treatment	3.3 units on a scale Standard Deviation 2.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 3 months

Population: All-treated set who had both a baseline and an EOT assessment.

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.

Outcome measures

Measure	EFI/ACT-385781A n=40 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Number of Participants With Improved, No Change, or Worsening of New York Heart Association Functional Class (NYHA FC) From Baseline to EOT. Improved	1 participants
Number of Participants With Improved, No Change, or Worsening of New York Heart Association Functional Class (NYHA FC) From Baseline to EOT. No change	35 participants
Number of Participants With Improved, No Change, or Worsening of New York Heart Association Functional Class (NYHA FC) From Baseline to EOT. Worsened	4 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 3 months

Population: All-treated set who had both a baseline and an EOT assessment.

Blood sampling for NT proBNP was performed at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.

Outcome measures

Measure	EFI/ACT-385781A n=36 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Change in N-terminal Pro-B-type Natriuretic Peptide (NT proBNP) From Baseline to EOT. Baseline	599.97 ng/L Standard Deviation 1164.21
Change in N-terminal Pro-B-type Natriuretic Peptide (NT proBNP) From Baseline to EOT. End of treatment	613.56 ng/L Standard Deviation 1155.90

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 3 months

Population: All-treated set who had both a baseline and an EOT assessment.

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.

Outcome measures

Measure	EFI/ACT-385781A n=38 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Change in Effectiveness Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT. Baseline	78.22 units on a scale Standard Deviation 12.61
Change in Effectiveness Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT. End of treatment	74.71 units on a scale Standard Deviation 17.60

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 3 months

Population: All-treated set who had both a baseline and an EOT assessment.

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.

Outcome measures

Measure	EFI/ACT-385781A n=38 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Change in Convenience Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT. Baseline	53.65 units on a scale Standard Deviation 15.78
Change in Convenience Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT. End of treatment	66.37 units on a scale Standard Deviation 17.04

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 3 months

Population: All-treated set who had both a baseline and an EOT assessment.

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.

Outcome measures

Measure	EFI/ACT-385781A n=38 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Change in Global Satisfaction Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT. Baseline	71.82 units on a scale Standard Deviation 18.35
Change in Global Satisfaction Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT. End of treatment	75.22 units on a scale Standard Deviation 15.58

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 3 months

Population: All-treated set.

Adverse events that led to discontinuation of study drug from the start of study treatment until the end of study treatment were recorded.

Outcome measures

Measure	EFI/ACT-385781A n=41 Participants EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Number of Participants With Adverse Events Leading to Discontinuation of Study Drug From Baseline to EOT.	0 participants

Adverse Events

EFI/ACT-385781A

Serious events: 7 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Measure	EFI/ACT-385781A n=41 participants at risk EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Infections and infestations Diverticulitis	2.4% 1/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set
Infections and infestations Device-related infection (pseudomonas)	2.4% 1/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set
General disorders Device connection issue	4.9% 2/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set
Cardiac disorders Right ventricular failure	2.4% 1/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set
General disorders Device damage	2.4% 1/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set
General disorders Device dislocation	2.4% 1/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set

Other adverse events

Measure	EFI/ACT-385781A n=41 participants at risk EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Nervous system disorders HEADACHE	29.3% 12/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set
Infections and infestations NASOPHARYNGITIS	17.1% 7/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set
Musculoskeletal and connective tissue disorders PAIN IN JAW	14.6% 6/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set
Vascular disorders FLUSHING	12.2% 5/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set
Respiratory, thoracic and mediastinal disorders DYSPNOEA	7.3% 3/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set
Respiratory, thoracic and mediastinal disorders EPISTAXIS	7.3% 3/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	7.3% 3/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set
Cardiac disorders PALPITATIONS	7.3% 3/41 • All adverse events (AEs) that occurred from the start of study treatment until 24 h after the end of study treatment were recorded. In addition, all serious AEs that occurred up to 30 days after the end of study treatment were also recorded. All treated set

Additional Information

Thomas Pfister, PhD, Senior Clinical Scientist

Actelion Pharmaceuticals Ltd

Phone: +41 61 565 5932

Email: thomas.pfister@actelion.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60