Upfront Combination Pulmonary Arterial Hypertension Therapy

Study Purpose

To evaluate the safety and efficacy of first-line combination therapy using riociguat with ambrisentan in patients with Pulmonary Arterial Hypertension (PAH).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03809156
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 4
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Calgary
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Naushad Hirani, MD
Principal Investigator Affiliation University of Calgary
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherIndustry
Overall Status Recruiting
Countries Canada
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Pulmonary Hypertension
Additional Details

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.

Arms & Interventions

Arms

Experimental: Combo Riociguat and Ambrisentan Therapy

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

Interventions

Drug: - Riociguat Oral Product

Dual therapy of Riociguat and Ambrisentan at initiation of treatment.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Peter Lougheed Center, Calgary, Alberta, Canada

Status

Recruiting

Address

Peter Lougheed Center

Calgary, Alberta, T1Y 6J4

Site Contact

Naushad Hirani, MD

403 943 4759

Vancouver, British Columbia, Canada

Status

Recruiting

Address

Vancouver General Hospital, The Lung Centre

Vancouver, British Columbia, V5Z 1M9

Site Contact

John Swiston, MD

swiston@mail.ubc.ca

(604) 875 4122

For more information, please contact PHA at Research@PHAssociation.org and refer to the terms of service below.

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