Status:
COMPLETED
Early Treatment of Borderline Pulmonary Arterial Hypertension Associated With Systemic Sclerosis (SSc-APAH)
Lead Sponsor:
Heidelberg University
Collaborating Sponsors:
GlaxoSmithKline
Conditions:
Systemic Sclerosis
Pulmonary Hypertension
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
Trial Design Patients with borderline PAH indicated by borderline mPAP values will be included in this single centre study. This clinical investigation is performed as a Proof-of-Concept (PoC) investi...
Detailed Description
Treatment naïve patients with SSc-APAH will be included in the investigator initiated trial (IIT) to assess efficacy and safety of ambrisentan. As patients life-expectancy after diagnosis of untreated...
Eligibility Criteria
Inclusion
- mPAP 21-24 mmHg, TPG \> 11mmHg, PAWP \<15 mmHg and/or
- 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
- Adult patients having completed his/her 18th birthday
- Patients with definite diagnosis of Systemic Sclerosis using the scleroderma criteria of the American Rheumatism Association
- SSc-disease duration \>3 years
- Able to understand and willing to sign the Informed Consent Form
- Negative pregnancy test at the start of the trial and appropriate contraception throughout the study for women with child-bearing potential.
Exclusion
- Any connective tissue diseases (CTD) other than SSc
- Pulmonary hypertension (PH) confirmed by right heart catheter (RHC) before enrolment, i.e. mPAP ≥25 mmHg at rest
- 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
- 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.
- 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.
- Known intolerance to ambrisentan or one of its excipients
- Clinically significant anemia (hemoglobin concentration of less than 75% of the lower limit of normal, LLN)
- Forced vital capacity (FVC) \<60%, forced expiratory volume in first second (FEV1) \<65%
- Severe interstitial lung disease, idiopathic pulmonary fibrosis
- Renal insufficiency (glomerular filtration rate \[GFR\] \<60 mL/min/1.73m2 for at least 3 months)
- Baseline values of hepatic aminotransferases (ALT and/or AST) \>3 x upper limit of normal (ULN)
- Systolic blood pressure \<85 mmHg;
- evidence of inadequately treated blood pressure \>160/90 mmHg and/or blood pressure during exercise \>220/120 mmHg
- Patients referred with clinically significant overt heart failure
- Clinically significant fluid retention
- 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)
- Known significant diastolic dysfunction associated with clinical heart failure
- Known coronary disease or significant valvular heart disease
- Known congenital heart defects such as single ventricle, transposition, Eisenmenger
- Known hypertrophic cardiomyopathy or left ventricular hypertrophy (interventricular septum thickness (IVS) or posterior wall thickness (PWD) \>1.2 cm)
- 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
- Pregnancy or lactation
Key Trial Info
Start Date :
July 1 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 31 2017
Estimated Enrollment :
38 Patients enrolled
Trial Details
Trial ID
NCT02290613
Start Date
July 1 2014
End Date
December 31 2017
Last Update
April 30 2020
Active Locations (1)
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1
Thoraxclinic at the University of Heidelberg
Heidelberg, Germany, 69126