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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02290613
• Date of registration: 31/10/2014
• Prospective Registration: No
• Primary sponsor: Heidelberg University
• Public title: Early Treatment of Borderline Pulmonary Arterial Hypertension Associated With Systemic Sclerosis (SSc-APAH) EDITA
• Scientific title: Early Treatment of Borderline Pulmonary Arterial Hypertension Associated With Systemic Sclerosis (SSc-APAH) A Randomized, Controlled, Double-blind, Parallel Group, Proof-of-concept Trial EDITA
• Date of first enrolment: July 1, 2014
• Target sample size: 38
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02290613
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Germany

Contacts

• Name: Ekkehard Grünig, MD
• Affiliation: Thoraxclinic at the University of Heidelberg

Key inclusion & exclusion criteria

Inclusion Criteria:

1. mPAP 21-24 mmHg, TPG > 11mmHg, PAWP <15 mmHg and/or

2. Exercise induced elevated mPAP-values >30 mmHg, PAWP <18 mmHg; TPG >15 mmHg, as
defined in Saggar et al. (2012) without left heart or severe lung disease or systemic
arterial hypertension

3. Adult patients having completed his/her 18th birthday

4. Patients with definite diagnosis of Systemic Sclerosis using the scleroderma criteria
of the American Rheumatism Association

5. SSc-disease duration >3 years

6. Able to understand and willing to sign the Informed Consent Form

7. Negative pregnancy test at the start of the trial and appropriate contraception
throughout the study for women with child-bearing potential.

Exclusion Criteria:

1. Any connective tissue diseases (CTD) other than SSc

2. Pulmonary hypertension (PH) confirmed by right heart catheter (RHC) before enrolment,
i.e. mPAP =25 mmHg at rest

3. Patients presenting normal mPAP values, that is mPAP<21 mmHg at rest, =30 mmHg during
exercise, PAWP >=15 mmHg at rest or <=18 mmHg during exercise

4. Ongoing or a history of >2 weeks of continued use of therapies that are considered
definitive PH treatment: endothelin receptor antagonists (ERA; e.g. bosentan,
ambrisentan), phosphodiesterase type 5 inhibitors (PDE5; e.g. sildenafil, tadalafil,
vardenafil), prostanoids (e.g. epoprostenol, treprostinil, iloprost, beraprost) and
soluble guanylate cyclase stimulator (e.g. Riociguat). Intermittent use of PDE5
inhibitors for male erectile dysfunction is permitted.

5. Except for diuretics and corticosteroids medical treatment should not be expected to
change 4 weeks prior inclusion into the study and during the entire 12-week study
period.

6. Known intolerance to ambrisentan or one of its excipients

7. Clinically significant anemia (hemoglobin concentration of less than 75% of the lower
limit of normal, LLN)

8. Forced vital capacity (FVC) <60%, forced expiratory volume in first second (FEV1) <65%

9. Severe interstitial lung disease, idiopathic pulmonary fibrosis

10. Renal insufficiency (glomerular filtration rate [GFR] <60 mL/min/1.73m2 for at least 3
months)

11. Baseline values of hepatic aminotransferases (ALT and/or AST) >3 x upper limit of
normal (ULN)

12. Systolic blood pressure <85 mmHg;

13. evidence of inadequately treated blood pressure >160/90 mmHg and/or blood pressure
during exercise >220/120 mmHg

14. Patients referred with clinically significant overt heart failure

15. Clinically significant fluid retention

16. Previous evidence or diagnosis of clinically relevant left heart disease, i.e. at
least one of the following: Previous echocardiography with estimated left ventricular
(LV) ejection fraction <50%, previous history of cardiogenic pulmonary edema,
increased size of left atrium (>50 mm)

17. Known significant diastolic dysfunction associated with clinical heart failure

18. Known coronary disease or significant valvular heart disease

19. Known congenital heart defects such as single ventricle, transposition, Eisenmenger

20. Known hypertrophic cardiomyopathy or left ventricular hypertrophy (interventricular
septum thickness (IVS) or posterior wall thickness (PWD) >1.2 cm)

21. Participation in any clinical drug trial within 4 weeks prior to screening of this
study and/or who is scheduled to receive another investigational medicinal product
(IMP) during the course of this study

22. Pregnancy or lactation



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Hypertension

Systemic Sclerosis

Intervention(s)

Drug: Placebo

Drug: Ambrisentan

Primary Outcome(s)

Mean Pulmonary Arterial Pressure Change From Baseline [Time Frame: baseline, 6 months]

Secondary Outcome(s)

Lung Function [Time Frame: baseline, 6 months]

Mean Pulmonary Arterial Pressure During Exercise Change From Baseline [Time Frame: baseline, 6 months]

6-Minute-walking Test [Time Frame: baseline, 6 months]

Quality of Life (SF-36) Questionnaire [Time Frame: baseline, 6 months]

WHO-functional Class [Time Frame: baseline]

Hemodynamics [Time Frame: change from baseline to 6 months]

Lung Function [Time Frame: baseline,6 months]

Borg Dyspnea Index [Time Frame: baseline, 6 months]

Hemodynamics [Time Frame: baseline , 6 months]

Hemodynamics [Time Frame: baseline, 6 months]

Echocardiography [Time Frame: baseline, 6 months]

Secondary ID(s)

2014-05ED

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

GlaxoSmithKline

Results

• Results available: Yes
• Date Posted: 30/04/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02290613