Status:
UNKNOWN
Upfront Combination Pulmonary Arterial Hypertension Therapy
Lead Sponsor:
University of Calgary
Collaborating Sponsors:
Bayer
Conditions:
Pulmonary Hypertension
Eligibility:
All Genders
18+ years
Phase:
PHASE4
Brief Summary
To evaluate the safety and efficacy of first-line combination therapy using riociguat with ambrisentan in patients with Pulmonary Arterial Hypertension (PAH).
Detailed Description
This is a prospective, multi-center, open-label, exploratory study with patients followed for a period of one year. The treatment duration period in this study begins at the initiation of ambrisentan ...
Eligibility Criteria
Inclusion
- Signed informed consent prior to initiation of any study mandated procedure;
- Males or females ≥ 18 years of age i. Women of childbearing potential must have a negative pre-treatment pregnancy test and must use reliable methods of contraception.
- ii. Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea for at least 1 year), or documented surgically or naturally sterile.
- Patients with symptomatic Functional Class III PAH in the following categories:
- i. Idiopathic (IPAH) ii. Familial (FPAH) iii. Associated with connective tissue disease iv. Associated with drugs or toxins;
- PAH diagnosed by right heart catheterization, defined as:
- i. Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg ii. PVR \> 3 mmHg/l/min (Wood units) or \> 240 dyn sec cm-5 iii. Pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg;
- 150 m ≤ 6 Minute Walk Test (6MWT) distance ≤ 480 m
Exclusion
- PAH associated with any other condition than those described in the inclusion criteria (patients with PAH associated with portal hypertension, HIV and CHD should not be included);
- PAH associated with thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders and splenectomy;
- Valvular disease with valvular lesions to be excluded by echocardiogram within 2 years prior to randomization (i.e., patients with tricuspid or pulmonary insufficiency secondary to PAH can be included);
- Restrictive lung disease: total lung capacity (TLC) \< 60% of normal predicted value;
- Obstructive lung disease: forced expiratory volume/forced vital capacity (FEV1/FVC) \< 0.5;
- Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C;
- Pregnancy or breast-feeding;
- Systolic blood pressure \< 95 mmHg;
- Body weight \< 40 kg;
- Hemoglobin \> 25% below the lower limit of the normal range;
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 1.5 times the upper limit of normal ranges;
- Renal insufficiency as defined by creatinine clearance \< 30 mL/min or on dialysis
- Treatment with phosphodiesterase type 5 inhibitors, any prostanoid (excluding acute administration during a catheterization procedure to test vascular reactivity) or with any other PH specific medication;
- Treatment or planned treatment with calcineurin-inhibitors (i.e., cyclosporine A and tacrolimus), CYP2C9 and CYP3A4 inhibitors (i.e., ketoconazole, fluconazole) within 1 week of study start;
- Treatment or planned treatment with nitrate drugs, short acting nitrate-containing medications, alpha blockers or protease inhibitors (i.e., ritonavir);
- Known hypersensitivity to ambrisentan, riociguat or any of their excipients;
- Patients with any contraindication to riociguat treatment or ERA treatment
- Patients with syncope, a rapid rate of symptom progression or with high or rising nt-BNP levels in the judgment of the investigators
- Any contraindications specified in the product monographs of either ambrisentan or riociguat, including:
- 1\. Patients at increased risk of hypotension with concomitant or underlying conditions such as coronary artery disease, hypovolemia, severe left ventricular outflow obstruction or autonomic dysfunction; patients with resting hypotension 2. Patients with history of serious hemoptysis or patients who have previously undergone bronchial arterial embolization 20. Patients with pulmonary veno-occlusive disease 21. Ongoing participation in any interventional clinical studies.
Key Trial Info
Start Date :
April 26 2016
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
January 31 2021
Estimated Enrollment :
20 Patients enrolled
Trial Details
Trial ID
NCT03809156
Start Date
April 26 2016
End Date
January 31 2021
Last Update
March 26 2020
Active Locations (2)
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1
Peter Lougheed Center
Calgary, Alberta, Canada, T1Y 6J4
2
Vancouver General Hospital, The Lung Centre
Vancouver, British Columbia, Canada, V5Z 1M9