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Early Treatment of Borderline Pulmonary Arterial Hypertension Associated With Systemic Sclerosis (SSc-APAH) (EDITA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02290613
Recruitment Status : Completed
First Posted : November 14, 2014
Results First Posted : April 30, 2020
Last Update Posted : April 30, 2020
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Prof. Dr. med. Ekkehard Gruenig, Heidelberg University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Systemic Sclerosis
Pulmonary Hypertension
Interventions Drug: Ambrisentan
Drug: Placebo
Enrollment 38
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Period Title: Overall Study
Started 19 19
Completed 17 15
Not Completed 2 4
Arm/Group Title Ambrisentan Verum Placebo Total
Hide Arm/Group Description

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Total of all reporting groups
Overall Number of Baseline Participants 19 19 38
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 19 participants 38 participants
58.8  (10.8) 54.9  (11.2) 56.8  (11.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 19 participants 38 participants
Female
16
  84.2%
14
  73.7%
30
  78.9%
Male
3
  15.8%
5
  26.3%
8
  21.1%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants
0
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Type of SSc  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 19 participants 38 participants
dcSSc
4
  21.1%
11
  57.9%
15
  39.5%
lcSSc
15
  78.9%
8
  42.1%
23
  60.5%
1.Primary Outcome
Title Mean Pulmonary Arterial Pressure Change From Baseline
Hide Description Determine whether mean pulmonary arterial pressure of SSc patients with borderline - PAH (mPAP 21 24 mmHg, TPG >11 mmHg) can be reduced by 3 mm Hg (absolute change baseline vs. 6 months; equals 15%) following treatment with ambrisentan 10 mg/die (initiated with 5 mg/die and elevated up to 10 mg/die) over 6 months (primary endpoint) compared to baseline and placebo.
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: mmHg
-1.0  (6.4) -0.73  (3.6)
2.Secondary Outcome
Title Mean Pulmonary Arterial Pressure During Exercise Change From Baseline
Hide Description Determine whether exercise induced elevated mean pulmonary arterial pressure-values (>30 mmHg without left heart or severe lung disease or systemic arterial hypertension) can be reduced by ambrisentan 10 mg/die over 6 months.
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 15 13
Mean (Standard Deviation)
Unit of Measure: mmHg
-0.73  (6.23) 1.08  (7.39)
3.Secondary Outcome
Title 6-Minute-walking Test
Hide Description [Not Specified]
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: meters
21.53  (34.6) -16.53  (77.32)
4.Secondary Outcome
Title Borg Dyspnea Index
Hide Description measured directly after 6 minute walking distance; The Borg dyspnea index is an standardized scale which reports the subjective feeling of exertion from 0 (no dyspnea) to 10 (maximal feeling of dyspnea).
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.62  (1.7) 0.08  (1.54)
5.Secondary Outcome
Title Quality of Life (SF-36) Questionnaire
Hide Description SF-36 Questionnaire; physical Summation score; All scores and subscores of the SF-36 questionnaire range from 0 (low quality of life) to 100 (high quality of life). The physical Summation score is a compound score including the physical dimensions of the SF-36.
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: units on a scale
-6.71  (12.17) 0.87  (16.01)
6.Secondary Outcome
Title Lung Function
Hide Description DLCo (diffusing capacity or transfer factor of the lung for carbon monoxide (CO))
Time Frame baseline,6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 13
Mean (Standard Deviation)
Unit of Measure: % of target value
1.19  (1.81) -0.44  (1.84)
7.Secondary Outcome
Title Lung Function
Hide Description DLCo (diffusing capacity or transfer factor of the lung for carbon monoxide (CO))
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: mmol/min/kPa
-0.32  (1.44) -0.45  (1.70)
8.Secondary Outcome
Title Lung Function
Hide Description FVC (forced vital capacity)
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: % of target
-3.31  (5.56) -1.04  (5.60)
9.Secondary Outcome
Title Lung Function
Hide Description FEV1 (forced expiratory volume in one second)
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 16 15
Mean (Standard Deviation)
Unit of Measure: Litres
-0.11  (0.21) -0.06  (0.20)
10.Secondary Outcome
Title Lung Function
Hide Description TLC (total lung capacity)
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 16 15
Mean (Standard Deviation)
Unit of Measure: Litres
-0.06  (0.37) -0.03  (0.36)
11.Secondary Outcome
Title Lung Function
Hide Description residual volume
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 16 15
Mean (Standard Deviation)
Unit of Measure: Litres
-0.03  (0.33) 0.05  (0.37)
12.Secondary Outcome
Title Echocardiography
Hide Description RA-area (right atrial area)
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: cm^2
1.65  (2.67) -0.47  (4.07)
13.Secondary Outcome
Title Echocardiography
Hide Description RV-area (right ventricular area)
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: cm^2
-0.15  (3.46) -0.8  (3.05)
14.Secondary Outcome
Title Echocardiography
Hide Description TAPSE (tricuspid annular plane systolic excursion)
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: cm
0.12  (0.41) -0.19  (0.54)
15.Secondary Outcome
Title Echocardiography
Hide Description sPAP (systolic pulmonary arterial pressure)
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: mmHg
-0.82  (4.46) -0.93  (6.08)
16.Secondary Outcome
Title WHO-functional Class
Hide Description

The World Health Organization functional class includes four categories with

  1. Patients with Pulmonary Hypertension but without any resulting limitation of physical activity.
  2. Patients with Pulmonary Hypertension resulting in slight limitation of physical activity.
  3. Patients with Pulmonary Hypertension resulting in marked limitation of physical activity.
  4. Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms.
Time Frame baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Measure Type: Count of Participants
Unit of Measure: Participants
FC II
17
 100.0%
13
  86.7%
FC III
0
   0.0%
2
  13.3%
17.Secondary Outcome
Title Hemodynamics
Hide Description right atrial pressure
Time Frame change from baseline to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: mmHg
0.82  (4.11) -0.2  (2.76)
18.Secondary Outcome
Title Hemodynamics
Hide Description pulmonary vascular resistance
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: Wood Units
-0.59  (0.79) 0.02  (0.76)
19.Secondary Outcome
Title Hemodynamics
Hide Description cardiac output (CO)
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: L/min
0.58  (1.17) -0.26  (1.11)
20.Secondary Outcome
Title Hemodynamics
Hide Description cardiac index (CI)
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 16 15
Mean (Standard Deviation)
Unit of Measure: L/min/m^2
0.36  (0.66) -0.31  (0.71)
21.Secondary Outcome
Title Hemodynamics
Hide Description PAWP (pulmonary arterial wedge pressure)
Time Frame baseline , 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 17 15
Mean (Standard Deviation)
Unit of Measure: mmHg
1.24  (5.31) 0.13  (3.20)
22.Secondary Outcome
Title Hemodynamics
Hide Description venous oxygen saturation (SvO2)
Time Frame baseline, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description:

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

Overall Number of Participants Analyzed 12 13
Mean (Standard Deviation)
Unit of Measure: % saturation
-2.79  (7.56) -3.48  (12.26)
Time Frame adverse Events were collected throughout the study from baseline to the 6 month-assessment and 30 days follow-up.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ambrisentan Verum Placebo
Hide Arm/Group Description

Study medication will be ambrisentan 10 mg (starting with 5 mg in the beginning of the study and then up-titrated to 10 mg/die).

Ambrisentan: Titration:

As common practice of the clinic, the patient will adapt the dose from 5 mg to 10 mg after 1 to 4 weeks according to tolerability and after consultation (by phone or personally) with one of the investigators.

Additionally, at each study visit the investigator needs to decide, based on the patient's well-being, patients´ assessment, safety parameters, and tolerance of ambrisentan, if the study medication should be modified. The respective decision (increase, maintain or decrease dose) must be documented.

Maximum dose allowed: not to exceed 10 mg/die.

Administration:

Ambrisentan and placebo will be administered orally with or without food intake.

Placebo tablet

Placebo: Placebo tablet (one to two tablets corresponding to one to two verum tablets)

All-Cause Mortality
Ambrisentan Verum Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)      0/19 (0.00%)    
Hide Serious Adverse Events
Ambrisentan Verum Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/19 (5.26%)      5/19 (26.32%)    
Blood and lymphatic system disorders     
Lymphangitis *  0/19 (0.00%)  0 1/19 (5.26%)  1
Cardiac disorders     
Angina Pectoris *  0/19 (0.00%)  0 1/19 (5.26%)  1
Coronary artery disease *  0/19 (0.00%)  0 1/19 (5.26%)  1
Gastrointestinal disorders     
Gastrointestinal infection *  0/19 (0.00%)  0 1/19 (5.26%)  1
Musculoskeletal and connective tissue disorders     
Lower jaw fracture *  1/19 (5.26%)  1 0/19 (0.00%)  0
Raynaud *  0/19 (0.00%)  0 1/19 (5.26%)  1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ambrisentan Verum Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/19 (89.47%)      17/19 (89.47%)    
Cardiac disorders     
Edema *  8/19 (42.11%)  8 4/19 (21.05%)  4
Coronary artery disease *  1/19 (5.26%)  1 3/19 (15.79%)  3
arterial hypotension *  2/19 (10.53%)  2 2/19 (10.53%)  2
Gastrointestinal disorders     
Diarrhea *  4/19 (21.05%)  4 2/19 (10.53%)  2
Nausea *  2/19 (10.53%)  2 3/19 (15.79%)  3
Nervous system disorders     
Headache *  6/19 (31.58%)  6 6/19 (31.58%)  6
Dizziness *  0/19 (0.00%)  0 6/19 (31.58%)  6
Paraesthesia *  4/19 (21.05%)  4 0/19 (0.00%)  0
Vascular disorders     
Epistaxis *  3/19 (15.79%)  3 1/19 (5.26%)  1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Prof. Dr. med. E. Grünig
Organization: Thoraxklinik Heidelberg gGmbH at Heidelberg University Hospital
Phone: +49 6221 396 ext 8053
EMail: ekkehard.gruenig@med.uni-heidelberg.de
Layout table for additonal information
Responsible Party: Prof. Dr. med. Ekkehard Gruenig, Heidelberg University
ClinicalTrials.gov Identifier: NCT02290613    
Other Study ID Numbers: 2014-05ED
First Submitted: October 31, 2014
First Posted: November 14, 2014
Results First Submitted: December 18, 2019
Results First Posted: April 30, 2020
Last Update Posted: April 30, 2020