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

• Sponsor: Actelion (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01431716
• Collaborator: (none)
• Enrollment: 42
• Locations: 8
• Arm: 1
• Duration (Months): 16
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.3

Study Details

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.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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)

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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 Outcome Measures

1. 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.

2. 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."

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. Chronic bleeding disorders

2. Central venous line infection within 90 days prior to screening and/or a history of recurring line infections

3. Women who are pregnant or breast-feeding

4. Participation in another clinical trial, except observational, or receipt of an investigational product within 30 days prior to randomization

5. 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

6. Known concomitant life-threatening disease other than PAH with a life expectancy < 12 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UZ Gasthuisberg	Leuven		Belgium	3000
2	University Health Network, Toronto TGH - 10 EN - 220	Toronto	Ontario	Canada	M5G 2N2
3	Sir Mortimer B Davis Jewish General Hospital	Montreal	Quebec	Canada	H3T 1 E2
4	Centre Hospitalier Universitaire	Caen		France	14033
5	Hôpital Antoine Béclère	Clamart Cedex		France	92141
6	Orsola Malpighi	Bologna		Italy	40138
7	VU Medisch Centrum (VUMC)	Amsterdam		Netherlands	1081 HV
8	Hospital Vall d'Hebron	Barcelona		Spain	8035

Sponsors and Collaborators

• Actelion

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Actelion
• ClinicalTrials.gov Identifier: NCT01431716
• Other Study ID Numbers: AC-066A301
• First Posted: Sep 12, 2011
• Last Update Posted: Jan 13, 2015
• Last Verified: Jan 1, 2015

• Additional relevant MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Epoprostenol

Study Results

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 Detail	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.

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

Baseline Characteristics

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Overall Participants	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.8 (13.9)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	38 92.7%
>=65 years	3 7.3%
Sex: Female, Male (Count of Participants)
Female	30 73.2%
Male	11 26.8%
Race/Ethnicity, Customized (participants) [Number]
White/Caucasian	18 43.9%
Black	2 4.9%
Asian	1 2.4%
Not Collected	20 48.8%
Region of Enrollment (participants) [Number]
France	20 48.8%
Canada	8 19.5%
Spain	2 4.9%
Belgium	5 12.2%
Netherlands	4 9.8%
Italy	2 4.9%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	36
Baseline	595.70 (237.14)
End of treatment	587.66 (248.44)

2. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	40
Baseline	498.1 (86.0)
End of treatment	492.8 (81.6)

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All treated set without imputation for missing values

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	41
Baseline	752.44 (260.91)
End of treatment	757.51 (296.82)

4. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All treated set without imputation for missing values

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	41
Baseline	51.9 (11.5)
End of treatment	51.7 (12.8)

5. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All treated set without imputation for missing values

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	41
Baseline	7.9 (4.6)
End of treatment	7.1 (4.6)

6. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	36
Baseline	10.3 (3.8)
End of treatment	10.1 (4.3)

7. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All treated set without imputation for missing values

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	41
Baseline	3.34 (0.71)
End of treatment	3.38 (0.81)

8. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	40
Baseline	4.0 (2.1)
End of treatment	3.3 (2.1)

9. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	40
Improved	1 2.4%
No change	35 85.4%
Worsened	4 9.8%

10. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	36
Baseline	599.97 (1164.21)
End of treatment	613.56 (1155.90)

11. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	38
Baseline	78.22 (12.61)
End of treatment	74.71 (17.60)

12. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	38
Baseline	53.65 (15.78)
End of treatment	66.37 (17.04)

13. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	38
Baseline	71.82 (18.35)
End of treatment	75.22 (15.58)

14. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

All-treated set.

Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
Measure Participants	41
Number [participants]	0 0%

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	All treated set
Arm/Group Title	EFI/ACT-385781A
Arm/Group Description	EFI/ACT-385781A administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump.
All Cause Mortality
	EFI/ACT-385781A
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	EFI/ACT-385781A
	Affected / at Risk (%)	# Events
Total	7/41 (17.1%)
Cardiac disorders
Right ventricular failure	1/41 (2.4%)
General disorders
Device connection issue	2/41 (4.9%)
Device damage	1/41 (2.4%)
Device dislocation	1/41 (2.4%)
Infections and infestations
Diverticulitis	1/41 (2.4%)
Device-related infection (pseudomonas)	1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	EFI/ACT-385781A
	Affected / at Risk (%)	# Events
Total	31/41 (75.6%)
Cardiac disorders
PALPITATIONS	3/41 (7.3%)
Infections and infestations
NASOPHARYNGITIS	7/41 (17.1%)
Musculoskeletal and connective tissue disorders
PAIN IN JAW	6/41 (14.6%)
PAIN IN EXTREMITY	3/41 (7.3%)
Nervous system disorders
HEADACHE	12/41 (29.3%)
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	3/41 (7.3%)
EPISTAXIS	3/41 (7.3%)
Vascular disorders
FLUSHING	5/41 (12.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.