Chronic Thromboembolic Pulmonary HypertensionPhase 2NCT03273257
Riociguat in Patients With Operable CTEPH Prior to Pulmonary Endarterectomy (PEA Bridging Study)
A Phase 2 study testing Riociguat and Pulmonary endarterectomy in people with Chronic Thromboembolic Pulmonary Hypertension and CTEPH, run by International CTEPH Association at 4 sites in 4 countries.
Trial summary
This is a randomised, double-blind, placebo-controlled, multicentre, multinational, prospective study in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) prior to pulmonary endarterectomy (PEA) with high preoperative pulmonary vascular resistance (PVR). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Thromboembolic Pulmonary Hypertension, CTEPH
- What is being tested?
- Riociguat and Pulmonary endarterectomy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 17 Aug 2018to 5 May 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Is a male or nonpregnant and nonlactating female patient aged from 18 to 80 years, both inclusive
- Is diagnosed with operable CTEPH and anticipating symptomatic and/or prognostic benefit from PEA
- Has pulmonary vascular resistance (PVR) >800 dyn·s·cm-5
- Has undergone right heart catheterisation not more than 180 days before randomisation visit
- Has been treated with anticoagulants for at least 90 days before randomisation visit
- Has ability to swallow oral medication
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- Has ability and willingness to participate and access the health facility
- Is capable of understanding the written informed consent and provides signed and witnessed written informed consent
- Female patient must be either surgically sterile, postmenopausal (no menses for the previous 12 months), or must be practicing an effective method of birth control as determined by the investigator (eg, oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or male partner with vasectomy or complete abstinence)
Who cannot join
- Has unstable disease in need of urgent PEA surgery as determined by the treating physician
- Has known hypersensitivity, allergic, or adverse reactions to riociguat or any of the excipients comprising riociguat tablets.
- Has known active hepatitis A IgM (HAV-IgM), hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCV Ab)
- Is human immunodeficiency virus positive
- Has pulmonary veno-occlusive disease
- Has symptomatic hypotension
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- Has symptomatic carotid disease
- Has significant coronary atherosclerotic disease in need of intervention
- Has severe left heart disease in need of intervention
- Has redo sternotomy
- Has received any background therapy for pulmonary arterial hypertension (PAH) in the preceding 30 days before randomisation visit including endothelin receptor antagonists (ERAs), phosphodiesterase 5 (PDE5) inhibitors, or prostanoids
- Is receiving nitrates, nitric oxide donors (e.g. amyl nitrite), ERAs, prostanoids, specific PDE5 inhibitors, nonspecific phosphodiesterase inhibitors (e.g. dipyridamole, theophylline)
- Is receiving strong cytochrome P450 (CYP) and P-glycoprotein/breast cancer resistance protein inhibitors
- Is receiving strong CYP3A inducers
- Has creatinine clearance <15 mL/min or on any form of dialysis
- Has severe hepatic impairment classified as Child-Pugh C
- Has received an investigational drug within the past 4 weeks before randomisation visit
- Is a lactating or pregnant (as demonstrated by a serum pregnancy test) woman, and not willing to take measures for not to become pregnant during the 3 months treatment study period and one month after the last dose of study drug administered
- Has smoked or used tobacco in any form, including snuff or chewing within 3 months prior to randomisation visit
- Has idiopathic interstitial pneumonitis
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
About this study
Official title: A Phase 2, Randomised, Double-Blind, Placebo-Controlled, Multicentre, Prospective Study to Assess Efficacy of Riociguat in Patients With Operable CTEPH Prior to Pulmonary Endarterectomy With High Preoperative Pulmonary Vascular Resistance
This is a randomised, double-blind, placebo-controlled, multicentre, multinational, prospective study in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) prior to pulmonary endarterectomy (PEA) with high preoperative pulmonary vascular resistance (PVR). Patients will be randomised in a 1:1 ratio to receive riociguat or matching placebo for 3 months before undergoing PEA. The primary objective of this study is to assess the efficacy of riociguat on preoperative PVR compared to placebo in patients with operable CTEPH.
- Being tested
- Riociguat, Placebo, Pulmonary endarterectomy
- Keywords
- Pulmonary endarterectomy, PEA, Medical therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiociguatDrug
Also called Adempas, BAY 63-2521
Riociguat will be initiated at 1 mg tid. The dosage will be increased by 0.5 mg at 2 week intervals based on tolerability as assessed by systolic blood pressure up to a maximum dose of 2.5 mg tid.
Downtitration to 0.5 mg tid is foreseen for patients with low optimal tolerability.
PlaceboDrug
Placebo will be given analogue to riociguat with matching tablets.
Pulmonary endarterectomyProcedure or surgery
Also called PEA
PEA will be performed at the end of medical treatment (Day 90)
| Study group | Role | What they receive |
|---|---|---|
| Riociguat | Active comparator | Patients will receive riociguat for 3 months followed by pulmonary endarterectomy. Receives: Drug: Riociguat; Procedure: Pulmonary endarterectomy |
| Placebo | Placebo comparator | Patients will receive placebo for 3 months followed by pulmonary endarterectomy. Receives: Drug: Placebo; Procedure: Pulmonary endarterectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Pulmonary Vascular Resistance (PVR) to Immediately Before Pulmonary Endarterectomy (Pre-PEA)
Pulmonary vascular resistance (PVR) will be assessed at baseline and immediately before pulmonary endarterectomy. The change in PVR will be assessed as percentage.
Measured: 90 days
Secondary outcomes (9)
Change From Baseline in Pulmonary Vascular Resistance (PVR) to 6 Months Post Pulmonary Endarterectomy (PEA)
Pulmonary vascular resistance (PVR) will be assessed at baseline and 6 months post pulmonary endarterectomy (PEA). The change in PVR will be assessed as percentage.
Measured: 270 days
Number of Patients With Either All-cause Death, PH-related Hospitalization, Need for PAH-targeted Therapy or WHO Functional Class Unchanged or Worse Between Randomization and 6 Months Post Pulmonary Endarterectomy (Composite Endpoint)
All deaths occurring post-randomization until the last visit will be included. All PH-related hospitalizations except the in-hospital care during and after pulmonary endarterectomy (PEA) from randomization until 6 months after PEA will be included.
The worst value for World Health Organization (WHO) functional class after treatment will be used.
Measured: 270 days
Intraoperative Circulatory Arrest Time
Circulatory arrest time will be measured in minutes
Measured: intraoperative
Number of Patients With Intraoperative Surgery-related Complications (Composite Endpoint)
The occurrence of any of the following complications will be assessed:
- Bleeding and/or blood loss >1 L in 12 hours
- Airway bleed with need for extracorporeal membrane oxygenation
- Any use of extracorporeal membrane oxygenation for respiratory or hemodynamic support, specified as veno-venous or veno-arterial
- Prolonged ventilation >96 hours
- Need for tracheostomy
- Need for drainage of pericardial effusion
- Neurological complications, ie, stroke, cerebral, subdural bleeding
- Reintubation or noninvasive ventilation for reperfusion response
- Hemoptysis requiring any intervention
- Renal failure requiring dialysis
- Wound infections
- Pneumonia
- Prolonged need for inotropic support (≥ 5 days)
Measured: intraoperative
Surgical Evaluation of Specimen: Stratification of Patients According to Ease of Dissection Plane
Classed as easier than normal (1); normal (2); more difficult than normal (3)
Measured: intraoperative
Surgical Evaluation of Specimen: Stratification of Patients According to Completeness of Disease Clearance
Classed as better than expected (1); as expected (2); worse than expected (3)
Measured: intraoperative
Surgical Evaluation of Specimen: Stratification of Patients According to Appearance of Clot and Vessel Wall
Classed as more solid than usual (1); normal (2); more friable than usual (3)
Measured: intraoperative
Number of Patients Who Died During the Course of the Study
All deaths occurring during the whole course of the study
Measured: 270 days
Patients Who Withdraw During the Randomized Treatment Phase
Only withdrawals after randomization but before PEA will be included
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2017
- Study start17 Aug 2018
- Primary completion5 May 2020
- Study completion5 May 2020
Why it stopped: The study was stopped due to slower than expected recruitment and the additional limitations on clinical research imposed by the COVID-19 pandemic, both of which made study completion within a reasonable timeframe appear unlikely.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Thromboembolic Pulmonary HypertensionStudies of the same condition, open and under way.
- 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
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- International CTEPH Association
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Jenkins, MD, Principal investigator, Papworth Hospital NHS Foundation Trust, Cambridge, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03273257
- Sponsor's protocol ID
- PEA Bridging Study
- Status last verified
- May 2021
- First submitted
- 25 Aug 2017
- Last updated
- 22 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: IPD sharing is not foreseen
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomised, Double-Blind, Placebo-Controlled, Multicentre, Prospective Study to Assess Efficacy of Riociguat in Patients With Operable CTEPH Prior to Pulmonary Endarterectomy With High Preoperative Pulmonary Vascular Resistance
- ClinicalTrials.gov ID
- NCT03273257
- Acronym / sponsor ID
- PEA Bridging Study
- Keywords
- Pulmonary endarterectomy, PEA, Medical therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped due to slower than expected recruitment and the additional limitations on clinical research imposed by the COVID-19 pandemic, both of which made study completion within a reasonable timeframe appear unlikely.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- International CTEPH AssociationUniversity, hospital or other
- Study start
- 17 Aug 2018 (actual)
- Primary completion
- 5 May 2020 (actual)
- Study completion
- 5 May 2020 (actual)
- First posted
- 6 Sep 2017 (actual)
- Results
- Posted 22 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomised, double-blind, placebo-controlled, multicentre, multinational, prospective study in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) prior to pulmonary endarterectomy (PEA) with high preoperative pulmonary vascular resistance (PVR). Patients will be randomised in a 1:1 ratio to receive riociguat or matching placebo for 3 months before undergoing PEA. The primary objective of this study is to assess the efficacy of riociguat on preoperative PVR compared to placebo in patients with operable CTEPH.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Riociguat | Active comparator | Drug: Riociguat, Procedure: Pulmonary endarterectomyPatients will receive riociguat for 3 months followed by pulmonary endarterectomy. |
| Placebo | Placebo comparator | Drug: Placebo, Procedure: Pulmonary endarterectomyPatients will receive placebo for 3 months followed by pulmonary endarterectomy. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Is a male or nonpregnant and nonlactating female patient aged from 18 to 80 years, both inclusive
- Is diagnosed with operable CTEPH and anticipating symptomatic and/or prognostic benefit from PEA
- Has pulmonary vascular resistance (PVR) >800 dyn·s·cm-5
- Has undergone right heart catheterisation not more than 180 days before randomisation visit
- Has been treated with anticoagulants for at least 90 days before randomisation visit
Key exclusion criteria (20 listed)
- Has unstable disease in need of urgent PEA surgery as determined by the treating physician
- Has known hypersensitivity, allergic, or adverse reactions to riociguat or any of the excipients comprising riociguat tablets.
- Has known active hepatitis A IgM (HAV-IgM), hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCV Ab)
- Is human immunodeficiency virus positive
- Has pulmonary veno-occlusive disease
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: Adempas, BAY 63-2521Riociguat will be initiated at 1 mg tid. The dosage will be increased by 0.5 mg at 2 week intervals based on tolerability as assessed by systolic blood pressure up to a maximum dose of 2.5 mg tid. Downtitration to 0.5 mg tid is foreseen for patients with low optimal tolerability. | Drug | Riociguat |
| PlaceboPlacebo will be given analogue to riociguat with matching tablets. | Drug | Placebo |
| Pulmonary endarterectomyAlso: PEAPEA will be performed at the end of medical treatment (Day 90) | Procedure or surgery | Placebo, Riociguat |
Primary outcome
Change From Baseline in Pulmonary Vascular Resistance (PVR) to Immediately Before Pulmonary Endarterectomy (Pre-PEA)
Time frame: 90 days
Pulmonary vascular resistance (PVR) will be assessed at baseline and immediately before pulmonary endarterectomy. The change in PVR will be assessed as percentage.
9 secondary outcomes
Change From Baseline in Pulmonary Vascular Resistance (PVR) to 6 Months Post Pulmonary Endarterectomy (PEA)
Time frame: 270 days
Number of Patients With Either All-cause Death, PH-related Hospitalization, Need for PAH-targeted Therapy or WHO Functional Class Unchanged or Worse Between Randomization and 6 Months Post Pulmonary Endarterectomy (Composite Endpoint)
Time frame: 270 days
Intraoperative Circulatory Arrest Time
Time frame: intraoperative
Number of Patients With Intraoperative Surgery-related Complications (Composite Endpoint)
Time frame: intraoperative
Surgical Evaluation of Specimen: Stratification of Patients According to Ease of Dissection Plane
Time frame: intraoperative
Surgical Evaluation of Specimen: Stratification of Patients According to Completeness of Disease Clearance
Time frame: intraoperative
Surgical Evaluation of Specimen: Stratification of Patients According to Appearance of Clot and Vessel Wall
Time frame: intraoperative
Number of Patients Who Died During the Course of the Study
Time frame: 270 days
Patients Who Withdraw During the Randomized Treatment Phase
Time frame: 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Website of the International CTEPH AssociationLink provided by the sponsor.
- Individual participant dataSharing planned: No. IPD sharing is not foreseen
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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.
David Jenkins, MD principal investigator
Papworth Hospital NHS Foundation Trust, Cambridge, UK
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Riociguat and Pulmonary endarterectomy in people with Chronic Thromboembolic Pulmonary Hypertension and CTEPH, run by International CTEPH Association at 4 sites in 4 countries.
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 9 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: stopped early, as of the sponsor's last update on 22 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, France, Germany, United Kingdom. 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?
Yes. Results are posted in the registry (first posted 22 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 in Pulmonary Vascular Resistance (PVR) to Immediately Before Pulmonary Endarterectomy (Pre-PEA) (time frame: 90 days). 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 22 Jun 2021.