Upfront Combination Pulmonary Arterial Hypertension Therapy

NCT ID: NCT03809156

Last Updated: 2020-03-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-26
• Study Completion Date: 2021-01-31

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 plus riociguat and will continue for 12 months. Patients will come to clinic for a visit at month 4 and 12. Assessments will include Right Heart Catheterization, 6 Minute walk test, cardiac MRI, questionnaires and nt-Pro-BNP.

Conditions

Pulmonary Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combo Riociguat and Ambrisentan Therapy

Riociguat Oral Product and Ambrisentan Oral Product to be given in combination to de novo (untreated) patients.

Group Type: EXPERIMENTAL

Riociguat Oral Product

Intervention Type: DRUG

Dual therapy of Riociguat and Ambrisentan at initiation of treatment.

Interventions

Riociguat Oral Product

Dual therapy of Riociguat and Ambrisentan at initiation of treatment.

Intervention Type: DRUG

Other Intervention Names

Ambrisentan Oral Product

Eligibility 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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Naushad Hirani, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

Peter Lougheed Center

Calgary, Alberta, Canada

Site Status: RECRUITING

Vancouver General Hospital, The Lung Centre

Vancouver, British Columbia, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Naushad Hirani, MD

Role: CONTACT

403 943 4759

Jean Marks, BN

Role: CONTACT

jean.marks@ahs.ca

(403) 943 4759

Facility Contacts

Naushad Hirani, MD

Role: primary

403 943 4759

John Swiston, MD

Role: primary

swiston@mail.ubc.ca

(604) 875 4122

Mami Okada

Role: backup

mami.okada@vch.ca

(604) 875 4111 ext. 69831

Other Identifiers

15-3056

Identifier Type: -

Identifier Source: org_study_id