Hypertension, PulmonaryPhase 2DYNAMICNCT02744339
Pharmacodynamic Effects of Riociguat in Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction
A Phase 2 study testing Riociguat in people with Hypertension, Pulmonary and Heart Failure With Normal Ejection Fraction, run by Medical University of Vienna at 1 site in Austria.
Trial summary
The primary objective of this study is to Assess the pharmacodynamic profile of riociguat in subjects with symptomatic pulmonary hypertension and heart failure with preserved ejection fraction The secondary objectives of this study are to Assess safety and tolerability of riociguat in this study population Assess… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypertension, Pulmonary, Heart Failure With Normal Ejection Fraction
- What is being tested?
- Riociguat
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 118 participants
- Where
- 1 siteAustria
- Study dates
- Mar 2016to Sep 2020
- Phase
- Phase 2
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 to <80 years of age at the time of informed consent (The lower age limit may be higher if legally required in participating countries.)
- Male and female subjects with symptomatic PH and HF-PEF (group 2 / 2.2 of Dana Point classification(4) and WHO class II to IV) (Other groups of PH, especially HF-REF, PAH, CTEPH, must have been ruled out according to accepted diagnostic procedures and guidelines, see section 5.1.2 Exclusion criteria.)
- PH-HF-PEF defined as:
- LVEF ≥50%, diagnosed by echocardiography or left heart catheterization (LHC) within 30 days before randomization
- PAPmean ≥25 mmHg at rest, measured by RHC
- PAWP >15 mmHg at rest, measured by RHC
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- Optimized therapy for hypertension
- The dose regimen of the background treatment must have been stable for >30 days before randomization. Diuretic therapy must have been stable for ≥1 week.
- RHC results for the definite diagnosis of PH not older than 12 weeks at Visit 1. RHC must have been performed in the participating center under standardized conditions
- CMRI must be performed at Visit 1 (baseline) or must not be older than 12 weeks with all parameters measured as listed in Section 7.3.3
- Women are eligible if not of childbearing potential, defined as:
- Postmenopausal women (i.e. last menstrual bleeding at least 2 years before randomization)
- Women with bilateral tubal ligation
- Women with bilateral ovariectomy
- Women with hysterectomy or, if of childbearing potential, women are eligible if
- A serum pregnancy test is negative at the pre-study visit, and The woman uses a combination of condoms and a safe and highly effective contraception method (hormonal contraception with implants or combined oral contraceptives, certain intrauterine devices) for the entire duration of the study.
- Able to understand and follow instructions and to participate in the study for its entire duration
- Written informed consent
Who cannot join
- PH in groups other than group 2.2 according to Dana Point classification.(4) In particular, PAH, CTEPH, and HF-REF must have been ruled out according to accepted diagnostic procedures and guidelines.
- Cardiac decompensation, with hospitalization or visit to the emergency department,
- ≤30 days before randomization
- Left heart disease because of to ischemic heart disease or dilated cardiomyopathy
- Resynchronization therapy at any time
- Need for intravenous (IV) diuretics ≤30 days before randomization
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- Treatment with inotropes or IV vasodilators ≤30 days before randomization
- Pre-treatment with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 (PDE5) inhibitors, or prostanoids ≤30 days before randomization, or with nitrates ≤7 days before randomization
- Subjects who medically require treatment with drugs that are not in line with the in- or exclusion criteria of this study or that are prohibited concomitant medications (see section 6.9) for this study
- Bronchial asthma or chronic obstructive pulmonary disease (COPD) with forced expiratory volume in 1 second (FEV1) <60% of predicted
- Restrictive lung disease with total lung capacity (TLC) <60% of predicted
- Subjects on oxygen therapy
- Severe congenital abnormalities of the lung, thorax, or diaphragm
- Clinically relevant hepatic dysfunction shown by:
- Aspartate aminotransferase (AST) ≥3 times the upper limit of normal (ULN) or
- Child Pugh stage B and C in cirrhotic subjects
- Severe renal impairment (glomerular filtration rate [GFR] <30mL/min/1.73 m2 calculated by the Modification of Diet in Renal Disease [MDRD] formula)
- Uncontrolled arterial hypertension (SBP >180 mmHg or diastolic blood pressure [DBP] >110 mmHg)
- SBP <110 mmHg at baseline
- Myocardial disease, such as ischemic or dilative infiltrative myocardial disease (i.e. amyloidosis, hypertrophic cardiomyopathy)
- Severe aortic or mitral stenosis, or any such stenosis with indication for surgery
- Coronary artery disease with angina of Canadian Cardiovascular Society (CCS) class III or IV or requiring nitrates, unstable angina, or acute myocardial infarction <90 days before randomization
- Reperfusion procedure (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) <90 days before randomization, or <21 days in case of a negative stress test effect after PCI
- Stroke with persistent neurological deficit
- Subjects positive for human immunodeficiency virus (HIV)
- Resting HR while awake of <50 beats per minute (BPM) or >105 BPM (in case of atrial fibrillation >110 BPM)
- Participation in another clinical study <90 days before randomization
- Subjects with a medical disorder, condition, or history thereof that in the opinion of the investigator would impair the subject's ability to participate or complete the 26-week study
- Subjects with underlying medical disorders with an anticipated life expectancy below 2 years because of a non-cardiac disease (e.g. active cancer disease with localized and / or metastasized tumor mass)
- Subjects with a history of multiple drug allergies
- Subjects with hypersensitivity to the investigational drug or any of the excipients
- Previous assignment to treatment during this study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of the Pharmacodynamic Effects of Riociguat in Subjects With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction in a Randomized, Double Blind, Placebo Controlled, Parallel Group, Multicenter Study
The primary objective of this study is to
- Assess the pharmacodynamic profile of riociguat in subjects with symptomatic pulmonary hypertension and heart failure with preserved ejection fraction
The secondary objectives of this study are to
- Assess safety and tolerability of riociguat in this study population
- Assess changes in dimensions of left and right ventricles and cardiac function parameters using cardiac magnetic resonance imaging
- Being tested
- Riociguat, Placebo
- Keywords
- PH-HFpEF
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiociguatDrug
Also called Adempas
Adempas up-titrated to max. 1.5mg TID
PlaceboDrug
Placebo sham-titrated TID
| Study group | Role | What they receive |
|---|---|---|
| Riociguat | Experimental | Riociguat up-titrated to a maximum of 1.5mg TID Receives: Drug: Riociguat |
| Placebo | Placebo comparator | Placebo sham-titrated TID Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline of cardiac output at rest, measured by right heart catheterization
Change from baseline of cardiac output at rest, measured by right heart catheterization after 26 weeks of study drug treatment
Measured: Baseline and 26 weeks after study drug treatment
Secondary outcomes (10)
Change from baseline in cardiac magnetic resonance imaging parameters
Change from baseline in right ventricular ejection fraction by cardiac magnetic resonance imaging
Measured: Baseline and 26 weeks after study drug treatment
Change from baseline in cardiac magnetic resonance imaging parameters
Change from baseline in right ventricular volume by cardiac magnetic resonance imaging
Measured: Baseline and 26 weeks after study drug treatment
Change from baseline in cardiac magnetic resonance imaging parameters
Change from baseline in left atrial area by cardiac magnetic resonance imaging
Measured: Baseline and 26 weeks after study drug treatment
Change from baseline in cardiac magnetic resonance imaging parameters
Change from baseline in right atrial area by cardiac magnetic resonance imaging
Measured: Baseline and 26 weeks after study drug treatment
Change from baseline in hemodynamic parameters other than cardiac output
Change from baseline in pulmonary vascular resistance by right heart catheterization
Measured: Baseline and 26 weeks after study drug treatment
Change from baseline in hemodynamic parameters other than cardiac output
Change from baseline in pulmonary arterial wedge pressure by right heart catheterization
Measured: Baseline and 26 weeks after study drug treatment
Change from baseline in hemodynamic parameters other than cardiac output
Change from baseline in transpulmonary gradient by right heart catheterization
Measured: Baseline and 26 weeks after study drug treatment
Change from baseline in hemodynamic parameters other than cardiac output
Change from baseline in systemic vascular resistance by right heart catheterization
Measured: Baseline and 26 weeks after study drug treatment
Change from baseline in WHO functional class
Measured: Baseline and 26 weeks after study drug treatment
Change from baseline in biomarker levels
Change from baseline in serum N-terminal prohormone B-type natriuretic peptide (NTproBNP)
Measured: Baseline and 26 weeks after study drug treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2016 (estimated)
- Study startMar 2016
- Primary completionAug 2020
- Study completionSep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypertension, PulmonaryStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, DBonderman, Medical University of Vienna
- Investigators
- Diana Bonderman, MD, Principal investigator, Medical University of ViennaJohannes Kastner, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02744339
- Sponsor's protocol ID
- RIO-40400
- Other IDs
- 2014-003055-60, 2014
- Acronym
- DYNAMIC
- Status last verified
- Nov 2020
- First submitted
- 18 Mar 2016
- Last updated
- 4 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Pharmacodynamic Effects of Riociguat in Subjects With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction in a Randomized, Double Blind, Placebo Controlled, Parallel Group, Multicenter Study
- ClinicalTrials.gov ID
- NCT02744339
- Acronym / sponsor ID
- DYNAMIC / RIO-40400
- Keywords
- PH-HFpEF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Mar 2016 (actual)
- Primary completion
- Aug 2020 (actual)
- Study completion
- Sep 2020 (actual)
- First posted
- 20 Apr 2016 (estimated)
- 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.
The primary objective of this study is to
- Assess the pharmacodynamic profile of riociguat in subjects with symptomatic pulmonary hypertension and heart failure with preserved ejection fraction
The secondary objectives of this study are to
- Assess safety and tolerability of riociguat in this study population
- Assess changes in dimensions of left and right ventricles and cardiac function parameters using cardiac magnetic resonance imaging
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Riociguat | Experimental | Drug: RiociguatRiociguat up-titrated to a maximum of 1.5mg TID |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo sham-titrated TID |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 18 to <80 years of age at the time of informed consent (The lower age limit may be higher if legally required in participating countries.)
- Male and female subjects with symptomatic PH and HF-PEF (group 2 / 2.2 of Dana Point classification(4) and WHO class II to IV) (Other groups of PH, especially HF-REF, PAH, CTEPH, must have been ruled out according to accepted diagnostic procedures and guidelines, see section 5.1.2 Exclusion criteria.)
- PH-HF-PEF defined as:
- Optimized therapy for hypertension
- The dose regimen of the background treatment must have been stable for >30 days before randomization. Diuretic therapy must have been stable for ≥1 week.
Key exclusion criteria (32 listed)
- PH in groups other than group 2.2 according to Dana Point classification.(4) In particular, PAH, CTEPH, and HF-REF must have been ruled out according to accepted diagnostic procedures and guidelines.
- Cardiac decompensation, with hospitalization or visit to the emergency department,
- ≤30 days before randomization
- Left heart disease because of to ischemic heart disease or dilated cardiomyopathy
- Resynchronization therapy at any time
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 |
|---|---|---|
| RiociguatAlso: AdempasAdempas up-titrated to max. 1.5mg TID | Drug | Riociguat |
| PlaceboPlacebo sham-titrated TID | Drug | Placebo |
Primary outcome
Change from baseline of cardiac output at rest, measured by right heart catheterization
Time frame: Baseline and 26 weeks after study drug treatment
Change from baseline of cardiac output at rest, measured by right heart catheterization after 26 weeks of study drug treatment
10 secondary outcomes
Change from baseline in cardiac magnetic resonance imaging parameters
Time frame: Baseline and 26 weeks after study drug treatment
Change from baseline in cardiac magnetic resonance imaging parameters
Time frame: Baseline and 26 weeks after study drug treatment
Change from baseline in cardiac magnetic resonance imaging parameters
Time frame: Baseline and 26 weeks after study drug treatment
Change from baseline in cardiac magnetic resonance imaging parameters
Time frame: Baseline and 26 weeks after study drug treatment
Change from baseline in hemodynamic parameters other than cardiac output
Time frame: Baseline and 26 weeks after study drug treatment
Change from baseline in hemodynamic parameters other than cardiac output
Time frame: Baseline and 26 weeks after study drug treatment
Change from baseline in hemodynamic parameters other than cardiac output
Time frame: Baseline and 26 weeks after study drug treatment
Change from baseline in hemodynamic parameters other than cardiac output
Time frame: Baseline and 26 weeks after study drug treatment
Change from baseline in WHO functional class
Time frame: Baseline and 26 weeks after study drug treatment
Change from baseline in biomarker levels
Time frame: Baseline and 26 weeks after study drug treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2020.
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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.
Diana Bonderman, MD principal investigator
Medical University of Vienna
Johannes Kastner, MD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Riociguat in people with Hypertension, Pulmonary and Heart Failure With Normal Ejection Fraction, run by Medical University of Vienna at 1 site in Austria.
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 18 inclusion and 32 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: finished, as of the sponsor's last update on 4 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline of cardiac output at rest, measured by right heart catheterization (time frame: Baseline and 26 weeks after study drug treatment). 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 4 Nov 2020.