Upfront Combination Pulmonary Arterial Hypertension Therapy

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03809156
• Date of registration: 09/01/2019
• Prospective Registration: No
• Primary sponsor: University of Calgary
• Public title: Upfront Combination Pulmonary Arterial Hypertension Therapy
• Scientific title: Upfront Riociguat and Ambrisentan Combination Therapy for Pulmonary Arterial Hypertension: A Safety and Efficacy Pilot Study
• Date of first enrolment: April 26, 2016
• Target sample size: 20
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT03809156
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Canada

Contacts

• Name: Naushad Hirani, MD

• Name: Naushad Hirani, MD
• Affiliation: University of Calgary

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Signed informed consent prior to initiation of any study mandated procedure;

2. 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.

3. 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;

4. 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;

5. 150 m = 6 Minute Walk Test (6MWT) distance = 480 m

Exclusion Criteria:

1. 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);

2. PAH associated with thyroid disorders, glycogen storage disease, Gaucher disease,
hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative
disorders and splenectomy;

3. 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);

4. Restrictive lung disease: total lung capacity (TLC) < 60% of normal predicted value;

5. Obstructive lung disease: forced expiratory volume/forced vital capacity (FEV1/FVC) <
0.5;

6. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C;

7. Pregnancy or breast-feeding;

8. Systolic blood pressure < 95 mmHg;

9. Body weight < 40 kg;

10. Hemoglobin > 25% below the lower limit of the normal range;

11. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the
upper limit of normal ranges;

12. Renal insufficiency as defined by creatinine clearance < 30 mL/min or on dialysis

13. 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;

14. 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;

15. Treatment or planned treatment with nitrate drugs, short acting nitrate-containing
medications, alpha blockers or protease inhibitors (i.e., ritonavir);

16. Known hypersensitivity to ambrisentan, riociguat or any of their excipients;

17. Patients with any contraindication to riociguat treatment or ERA treatment

18. Patients with syncope, a rapid rate of symptom progression or with high or rising
nt-BNP levels in the judgment of the investigators

19. 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.



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

Health Condition(s) or Problem(s) studied

Pulmonary Hypertension

Intervention(s)

Drug: Riociguat Oral Product

Primary Outcome(s)

Pulmonary Vascular resistance [Time Frame: 4 and 12 months]

Secondary Outcome(s)

RV function [Time Frame: 4 and 12 months]

Quality of Life Assessment [Time Frame: 4 and 12 months]

Survival [Time Frame: 12 months]

Dyspnea [Time Frame: 4 and 12 months]

Functional Class [Time Frame: 4 and 12 months]

Echocardiographic parameters [Time Frame: 4 and 12 months]

Clinical worsening [Time Frame: 12 months]

Exercise capacity [Time Frame: 4 and 12 months]

Hemodynamic Variables [Time Frame: 4 and 12 months]

NT-PRo-BNP [Time Frame: 4 and 12 Months]

Secondary ID(s)

15-3056

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Bayer