Pulmonary Arterial HypertensionPhase 3NCT04062565
Trial to Evaluate Parenteral Treprostinil and Riociguat on Right Ventriculo-vascular Coupling and Morphology in Those With Advanced PAH
A Phase 3 study testing Treprostinil Injectable Product and Riociguat Pill in people with Pulmonary Arterial Hypertension, run by University of Arizona at 1 site in United States.
Trial summary
The purpose of this study is to determine if there is a greater effect to patients with advanced pulmonary arterial hypertension (PAH) by using a combination of two drugs, Treprostinil and Riociquat versus Treprostinil alone Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Treprostinil Injectable Product and Riociguat Pill
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Mar 2019to 31 Dec 2025
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- WHO Category I PAH
- Resting mPAP ≥ 25 mmHg with a wedge pressure of ≤ 15mmHg during right heart catheterization.
- Need for parenteral TRE as determined by the PH specialist caring for the patient
Who cannot join
- Patients with a mean arterial pressure <60, and/or requiring vasopressor support
- Patients whom expected device (i.e. ECMO, RVAD) assistance or early pulmonary transplantation (within 3 months) seems inevitable
- Patients with a left ventricular ejection fraction <50% or clinical, echocardiographic, and/or catheterization data consistent with heart failure with preserved ejection fraction (HFpEF) and/or moderate-severe aortic or mitral valve abnormality
- Patients with severe restrictive lung disease (FVC<70% predicted) and/or obstructive lung disease (FEV1 <70% predicted and FEV1/FVC <70%).
- Patients with a history of pulmonary embolism within the last three months or evidence of chronic pulmonary embolism.
- Patients with a known contraindication to right heart catheterization.
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- Patients whom have received active or previous pulmonary vasoactive medication within the previous 12 weeks.
- PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis.
- Pulmonary Hypertension belonging to groups 2 to 5 of the WHO classification.
- Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
- Estimated creatinine clearance < 30 mL/min
- Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal.
- Hemoglobin < 75% of the lower limit of the normal range.
- Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements.
- Pregnant or breast-feeding.
- Females must either abstain from intercourse (when it is in line with their preferred and usual lifestyle), or
- Use 2 medically acceptable, highly effective forms of contraception for the duration of study, and at least 30 after discontinuing study drug.
- Known concomitant life-threatening disease with a life expectancy < 12 months.
- Body weight < 40 kg and/or >150 kg.
- Any condition that prevents compliance with the protocol or adherence to therapy.
- Concurrent therapy with strong CYP3A4 inhibitors/inducers (i.e. protease inhibitors, azole antibiotics, macrolides), theophylline, and any medication in the PI's opinion may substantially potentiate the hypotensive effect of RIO.
- Treatment with nitrates of any kind within the 4 weeks prior to enrollment.
- Known hypersensitivity to drugs of the same class as TRE and/or RIO, or any of their excipients.
- Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization.
- Recent (<6 months) hemoptysis and/or history of severe hemoptysis requiring intervention (bronchial artery embolization).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Arizona
Tucson, Arizona, 85724
Valerie Bloss, MS, 520-626-8305, vbloss@email.arizona.edu
Franz Rischard, DO
About this study
Official title: A Prospective Trial to Evaluate Up-front Parenteral Treprostinil and Riociguat on Right Ventriculo-vascular Coupling and Morphology in Patients With Advanced Pulmonary Arterial Hypertension (IIR-3810)
The purpose of this study is to determine if there is a greater effect to patients with advanced pulmonary arterial hypertension (PAH) by using a combination of two drugs, Treprostinil and Riociquat versus Treprostinil alone
Read the detailed description
The purpose of this study is to evaluate the combined effect of parenteral treprostinil (TRE) and riociguat (RIO) versus parenteral TRE alone on right ventricular (RV)-pulmonary artery (PA) interaction (RVPA coupling) and global RV function in patients with advanced pulmonary arterial hypertension (PAH).
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Treprostinil Injectable Product, Riociguat Pill
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treprostinil Injectable ProductDrug
Also called Remodulin
Injection
Riociguat PillDrug
Also called Adempas
Tablet
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Treprostinil and Riociguat Receives: Drug: Treprostinil Injectable Product; Drug: Riociguat Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in stroke volume/end systolic volume (SV/ESV)
Change in stroke volume/end systolic volume (SV/ESV)
Measured: Baseline to 3 months
Secondary outcomes (12)
Change in pulmonary and cardiac pressures
Increase or decrease in pressures
Measured: Baseline to 3 months
Change in pulmonary blood flow
Increase or decrease in pulmonary blood flow
Measured: Baseline to 3 months
Change in end-systolic elastance/arterial elastance (Ees/Ea)
Change in the interaction of the right heart and lung blood vessels
Measured: Baseline to 3 months
Change in Right Ventricle (RV) diastolic stiffness (Beta)
Change in how stiff the wall of the right heart is at the end of relaxation
Measured: Baseline to 3 months
Change in 6 minute walk distance
Change in how far a participant can walk during a self paced 6 minute walk test
Measured: Baseline to 3 months
Change in brain natriuretic peptide (BNP)
Change in biomarker BNP that examines stretch on the right heart
Measured: Baseline to 3 months
Change in magnetic resonance imaging (MRI) right ventricle volumes
Change in the volume ejected per beat and the end systolic and diastolic values of the right heart
Measured: Baseline to 3 months
Change in Cardio pulmonary Exercise Testing (CPET)
Change in how much oxygen the body consumes at peak exercise
Measured: 3 months
Change in derived VO2 max
Change in how much oxygen the body consumes at peak exercise
Measured: 3 months
Change in derived Ve/VCO2
Change in how much oxygen the body consumes at peak exercise
Measured: 3 months
Change in adverse event profile
Change in side effects or other adverse events between combination therapy and historical control
Measured: Baseline to 3 months
Change in composite time to clinical worsening
Difference relative to historical control in the time from diagnosis to followup, hospitalization, death or transplant
Measured: Baseline to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2019
- Study start25 Mar 2019
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All participants will receive Treprostinil 2-3 times per day as tolerated. * Subsequently, participants will receive Riociguat at 0.5 mg taken orally three times a day. * Participants will receive the first dose inpatient prior to discharge. * Participants will continue on a 2 ng/kg/min increase every other day for one week. * Riociguat will subsequently be increased by 0.5 mg taken orally three times a day the following week as tolerated. * Increases in Treprostinil and Riociguat will then alternate weeks such that only one medication is changed per week.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Franz Rischard, DO, University of Arizona
- Investigators
- Franz Rischard, DO, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04062565
- Sponsor's protocol ID
- 1812168816
- Status last verified
- Feb 2025
- First submitted
- 29 Mar 2019
- Last updated
- 20 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Trial to Evaluate Up-front Parenteral Treprostinil and Riociguat on Right Ventriculo-vascular Coupling and Morphology in Patients With Advanced Pulmonary Arterial Hypertension (IIR-3810)
- ClinicalTrials.gov ID
- NCT04062565
- Acronym / sponsor ID
- 1812168816
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Study start
- 25 Mar 2019 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 20 Aug 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.
The purpose of this study is to determine if there is a greater effect to patients with advanced pulmonary arterial hypertension (PAH) by using a combination of two drugs, Treprostinil and Riociquat versus Treprostinil alone
Detailed description
The purpose of this study is to evaluate the combined effect of parenteral treprostinil (TRE) and riociguat (RIO) versus parenteral TRE alone on right ventricular (RV)-pulmonary artery (PA) interaction (RVPA coupling) and global RV function in patients with advanced pulmonary arterial hypertension (PAH).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All participants will receive Treprostinil 2-3 times per day as tolerated. * Subsequently, participants will receive Riociguat at 0.5 mg taken orally three times a day. * Participants will receive the first dose inpatient prior to discharge. * Participants will continue on a 2 ng/kg/min increase every other day for one week. * Riociguat will subsequently be increased by 0.5 mg taken orally three times a day the following week as tolerated. * Increases in Treprostinil and Riociguat will then alternate weeks such that only one medication is changed per week.
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Treprostinil Injectable Product, Drug: Riociguat PillTreprostinil and Riociguat |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- WHO Category I PAH
- Resting mPAP ≥ 25 mmHg with a wedge pressure of ≤ 15mmHg during right heart catheterization.
- Need for parenteral TRE as determined by the PH specialist caring for the patient
Key exclusion criteria (25 listed)
- Patients with a mean arterial pressure <60, and/or requiring vasopressor support
- Patients whom expected device (i.e. ECMO, RVAD) assistance or early pulmonary transplantation (within 3 months) seems inevitable
- Patients with a left ventricular ejection fraction <50% or clinical, echocardiographic, and/or catheterization data consistent with heart failure with preserved ejection fraction (HFpEF) and/or moderate-severe aortic or mitral valve abnormality
- Patients with severe restrictive lung disease (FVC<70% predicted) and/or obstructive lung disease (FEV1 <70% predicted and FEV1/FVC <70%).
- Patients with a history of pulmonary embolism within the last three months or evidence of chronic pulmonary embolism.
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 |
|---|---|---|
| Treprostinil Injectable ProductAlso: RemodulinInjection | Drug | Experimental |
| Riociguat PillAlso: AdempasTablet | Drug | Experimental |
Primary outcome
Change in stroke volume/end systolic volume (SV/ESV)
Time frame: Baseline to 3 months
Change in stroke volume/end systolic volume (SV/ESV)
12 secondary outcomes
Change in pulmonary and cardiac pressures
Time frame: Baseline to 3 months
Change in pulmonary blood flow
Time frame: Baseline to 3 months
Change in end-systolic elastance/arterial elastance (Ees/Ea)
Time frame: Baseline to 3 months
Change in Right Ventricle (RV) diastolic stiffness (Beta)
Time frame: Baseline to 3 months
Change in 6 minute walk distance
Time frame: Baseline to 3 months
Change in brain natriuretic peptide (BNP)
Time frame: Baseline to 3 months
Change in magnetic resonance imaging (MRI) right ventricle volumes
Time frame: Baseline to 3 months
Change in Cardio pulmonary Exercise Testing (CPET)
Time frame: 3 months
Change in derived VO2 max
Time frame: 3 months
Change in derived Ve/VCO2
Time frame: 3 months
Change in adverse event profile
Time frame: Baseline to 3 months
Change in composite time to clinical worsening
Time frame: Baseline to 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2025.
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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.
Franz Rischard, DO principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Treprostinil Injectable Product and Riociguat Pill in people with Pulmonary Arterial Hypertension, run by University of Arizona at 1 site in United States.
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 3 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 20 Feb 2025. 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 United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Valerie Boss, MS (520-626-8305, vbloss@email.arizona.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in stroke volume/end systolic volume (SV/ESV) (time frame: Baseline to 3 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 20 Feb 2025.