Pulmonary HypertensionPhase 4NCT03809156
Upfront Combination Pulmonary Arterial Hypertension Therapy
A Phase 4 study testing Riociguat Oral Product in people with Pulmonary Hypertension, run by University of Calgary at 2 sites in Canada.
Trial summary
To evaluate the safety and efficacy of first-line combination therapy using riociguat with ambrisentan in patients with Pulmonary Arterial Hypertension (PAH). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- Riociguat Oral Product
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesCanada
- Study dates
- 26 Apr 2016to 31 Jan 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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:
- 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:
- 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
Who cannot join
- 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;
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- 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.
Trial locations and contacts
2 sites in 1 country.
Naushad Hirani, MD contact
Canada2 sites, 2 recruiting
- Recruiting
Peter Lougheed Center
Calgary, Alberta, T1Y 6J4
Naushad Hirani, MD, 403 943 4759
- Recruiting
Vancouver General Hospital, The Lung Centre
Vancouver, British Columbia, V5Z 1M9
John Swiston, MD, (604) 875 4122, swiston@mail.ubc.ca
Mami Okada, (604) 875 4111 ext. 69831, mami.okada@vch.ca
About this study
Official title: Upfront Riociguat and Ambrisentan Combination Therapy for Pulmonary Arterial Hypertension: A Safety and Efficacy Pilot Study
To evaluate the safety and efficacy of first-line combination therapy using riociguat with ambrisentan in patients with Pulmonary Arterial Hypertension (PAH).
Read the 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
- Being tested
- Riociguat Oral Product
- Keywords
- Pulmonary Hypertension
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Riociguat Oral ProductDrug
Also called Ambrisentan Oral Product
Dual therapy of Riociguat and Ambrisentan at initiation of treatment.
| Study group | Role | What they receive |
|---|---|---|
| Combo Riociguat and Ambrisentan Therapy | Experimental | Riociguat Oral Product and Ambrisentan Oral Product to be given in combination to de novo (untreated) patients. Receives: Drug: Riociguat Oral Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulmonary Vascular resistance
Change from baseline to month 4 and month 12 in pulmonary vascular resistance (PVR) as assessed by Right Heart Catheterization.
Measured: 4 and 12 months
Secondary outcomes (10)
Hemodynamic Variables
Change in hemodynamic variables (mPAP, RAP, CI) from baseline to month 4 and month 12 as assessed by Right Heart Catheterization.
Measured: 4 and 12 months
Echocardiographic parameters
Change in echocardiographic parameters (TAPSE, RV strain, Tei index, Left ventricular Eccentricity index, RV:LV area ratio) as assessed by Echocardiogram.
Measured: 4 and 12 months
RV function
Change from baseline to month 4 in RV function as assessed by cardiac MRI.
Measured: 4 and 12 months
NT-PRo-BNP
Change from baseline NT-PRo-BNP value from baseline to month 4 and month 12
Measured: 4 and 12 Months
Exercise capacity
Change from baseline to month 4 and month 12 in exercise capacity assessed by the 6 minute walk test
Measured: 4 and 12 months
Dyspnea
Change from baseline to month 4 and month 12 in dyspnea as assessed by study questionnaire.
Measured: 4 and 12 months
Quality of Life Assessment
Change from baseline to month 4 and month 12 in quality of life as assessed by study questionnaire.
Measured: 4 and 12 months
Functional Class
Change from baseline to month 4 and month 12 in functional class as assessed by study questionnaire.
Measured: 4 and 12 months
Survival
Survival at 12 months
Measured: 12 months
Clinical worsening
Time to clinical worsening over 12 months
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2019
- Study start26 Apr 2016
- Primary completion31 Dec 2020 (estimated)
- Study completion31 Jan 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Naushad Hirani, MD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03809156
- Sponsor's protocol ID
- 15-3056
- Status last verified
- Mar 2020
- First submitted
- 9 Jan 2019
- Last updated
- 26 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Upfront Riociguat and Ambrisentan Combination Therapy for Pulmonary Arterial Hypertension: A Safety and Efficacy Pilot Study
- ClinicalTrials.gov ID
- NCT03809156
- Acronym / sponsor ID
- 15-3056
- Conditions
- Pulmonary Hypertension
- Keywords
- Pulmonary Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- 26 Apr 2016 (actual)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 31 Jan 2021 (estimated)
- First posted
- 18 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combo Riociguat and Ambrisentan Therapy | Experimental | Drug: Riociguat Oral ProductRiociguat Oral Product and Ambrisentan Oral Product to be given in combination to de novo (untreated) patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
- Patients with symptomatic Functional Class III PAH in the following categories:
- PAH diagnosed by right heart catheterization, defined as:
- 150 m ≤ 6 Minute Walk Test (6MWT) distance ≤ 480 m
Key exclusion criteria (20 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Riociguat Oral ProductAlso: Ambrisentan Oral ProductDual therapy of Riociguat and Ambrisentan at initiation of treatment. | Drug | Combo Riociguat and Ambrisentan Therapy |
Primary outcome
Pulmonary Vascular resistance
Time frame: 4 and 12 months
Change from baseline to month 4 and month 12 in pulmonary vascular resistance (PVR) as assessed by Right Heart Catheterization.
10 secondary outcomes
Hemodynamic Variables
Time frame: 4 and 12 months
Echocardiographic parameters
Time frame: 4 and 12 months
RV function
Time frame: 4 and 12 months
NT-PRo-BNP
Time frame: 4 and 12 Months
Exercise capacity
Time frame: 4 and 12 months
Dyspnea
Time frame: 4 and 12 months
Quality of Life Assessment
Time frame: 4 and 12 months
Functional Class
Time frame: 4 and 12 months
Survival
Time frame: 12 months
Clinical worsening
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Naushad Hirani, MD contact
Naushad Hirani, MD principal investigator
University of Calgary
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Riociguat Oral Product in people with Pulmonary Hypertension, run by University of Calgary at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Naushad Hirani, MD (403 943 4759), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pulmonary Vascular resistance (time frame: 4 and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2020.