CTEPHPhase 3NCT04730037
Clinical Trial to Investigate Safety and Efficacy of Edoxaban in Patients With CTEPH (KABUKI)
A Phase 3 study testing Edoxaban and Warfarin Potassium in people with CTEPH, run by Kyushu University at 1 site in Japan.
Trial summary
This is phase III trial to evaluate whether edoxaban, a direct factor Xa inhibitor, is noninferior to warfarin in preventing worsening of chronic thromboembolic pulmonary hypertension (CTEPH). Read more about this study
- Who is it for?
- Ages 20 to 85 years
- Conditions the study is for
- CTEPH
- What is being tested?
- Edoxaban and Warfarin Potassium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 1 siteJapan
- Study dates
- 23 Mar 2021to 27 Jun 2023
- Phase
- Phase 3
- 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 20 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient who once* diagnosed with CTEPH based on at least 2 imaging study (VQ scan, CT pulmonary angiogram, or catheter-based pulmonary angiogram) and hemodynamic criteria (MPAP >=25 mmHg and PAWP =< 15 mmHg). *Patients treated with PEA, BPA, or vasodilators, who do not meet hemodynamic criteria at the registration, are eligible.
- Patients who are not planned to require increased / changed / discontinuation of PEA, BPA, or pulmonary vasodilators within 12months
- Stable administration of vitamin K antagonists
- WHO functional class I-III
- Patients who meet A) B)and C) by 90 days prior to baseline. A)No addition, reduction, or change of endothelin antagonists, soluble guanylate cyclase stimulants, phosphodiesterase-5 inhibitors, prostacyclin, and its derivatives, or calcium antagonists. B)Appropriate anticoagulants have been continued. C)No BPA has been done.
- Patients who have not undergone PEA from 180 days prior to baseline right heart catheterization to the start date of study drug administration
- Patients with a 6-minute walking distance >=150m
Who cannot join
- Patients with severe lung disease (FEV1.0/FVC < 60% or %TLC < 60%)
- Patients with acute or chronic disabilities that interfere with clinical trial requirements
- Patients with acute symptomatic PE within 180 days prior to the start of study drug administration
- Patients with congenital heart disease who have not undergone radical surgery
- Patients who cannot provide informed consent due to mental disorders, dementia, or other illnesses
- Patients with advanced cancer
Show all 15Show fewer
- Patients with a life expectancy of less than 1 year
- Patients with active hemorrhagic lesions
- Patients with comorbidities requiring vitamin K antagonist
- Patients receiving other study drug within 30 days prior to randomization
- Patients with renal dysfunction (Ccr 15 mL/min)
- Patients with liver dysfunction (Child-Pugh B or C)
- Females of reproductive age not using an acceptable form of contraception/Pregnant/Breastfeeding
- Patients contraindicated for edoxaban or warfarin
- Patients with hypersensitivity to any of the drug
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Investigator-initiated, Multicenter, Phase 3, Randomized, Single-blind, Double-dummy, Parallel-group Study of Evaluate the Efficacy and Safety of Edoxaban Versus Warfarin (Vitamin K Antagonist) in Subjects With Chronic Thromboembolic Pulmonary Hypertension Taking Warfarin (Vitamin K Antagonist) at Baseline: KABUKI
This is phase III trial to evaluate whether edoxaban, a direct factor Xa inhibitor, is noninferior to warfarin in preventing worsening of chronic thromboembolic pulmonary hypertension (CTEPH).
- Conditions
- CTEPH
- Being tested
- Edoxaban, Warfarin Potassium, Warfarin Potassium placebo, Edoxaban placebo
- Keywords
- Edoxaban, DOAC, Wafrarin, Anticoagulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EdoxabanDrug
- Edoxaban 30 mg/60 mg tablet according to body weight. 60 kg or less: 30 mg once daily, over 60 kg: 60 mg once daily, reduced to 30 mg once daily depending on renal function and concomitant medications
Warfarin PotassiumDrug
- Warfarin K 1 mg tablets once daily (Dose adjusted with target PT-INR of 1.5-2.5)
Warfarin Potassium placeboDrug
- Warfarin K 1 mg placebo tablets once daily
Edoxaban placeboDrug
- Edoxaban 30 mg/60 mg placebo tablet according to body weight. 60 kg or less: 30 mg once daily, over 60 kg: 60 mg once daily, reduced to 30 mg once daily depending on renal function and concomitant medications
| Study group | Role | What they receive |
|---|---|---|
| Edoxaban group | Active comparator | Not described Receives: Drug: Edoxaban; Drug: Warfarin Potassium placebo |
| Warfarin group | Active comparator | Not described Receives: Drug: Warfarin Potassium; Drug: Edoxaban placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of 1-year resting PVR to baseline resting PVR
Measured: Week 48 of treatment
Secondary outcomes (5)
Percentage of cases with worsening of CTEPH
Measured: Throughout the study duration(up to week48)
Change from baseline in 6-minute walk distance
Measured: Week16, 32, 48 of treatment
Change from baseline in WHO functional class
Measured: Week16, 32, 48 of treatment
Change from baseline in NT-proBNP
Measured: Week16, 32, 48 of treatment
Percentage of cases with clinically relavant bleeding (ISTH 2015 definition)
Measured: Throughout the study duration(up to week48)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2021
- Study start23 Mar 2021
- Primary completion30 Mar 2023
- Study completion27 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for CTEPHStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyushu University
- Sponsor type
- University, hospital or other
- Collaborators
- Daiichi Sankyo Co., Ltd.
- Responsible party
- Principal investigator, Kohtaro Abe, Kyushu University
- Investigators
- Kohtaro Abe, Principal investigator, Kyushu University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04730037
- Sponsor's protocol ID
- CTR225-01
- Status last verified
- Oct 2023
- First submitted
- 25 Jan 2021
- Last updated
- 5 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data are available upon reasonable request. The deidentified participant data collected in this study will be shared with manufacturers of investigational drugs, Ministry of Health, Labor and Welfare, and regulatory authorities related to pharmaceutical affairs. Data are attributed to Kyushu University and Daiichi Sankyo Co., Ltd. Protocols, informed consent form, and statistical analysis plans will be shared upon reasonable request. Contact: abe.kotaro.232@m.kyushu-u.ac.jp
Publications
Hosokawa K, Abe K, Tsutsui H. Use of direct oral anticoagulants prevents increase in pulmonary vascular resistance and incidence of clinical worsening in patients with chronic thromboembolic pulmonary hypertension. Thromb Res. 2019 Aug;180:43-46. doi: 10.1016/j.thromres.2019.05.018. Epub 2019 May 31. No abstract available.
PubMed 31200342Hosokawa K, Abe K, Kishimoto J, Kobayakawa Y, Todaka K, Tamura Y, Tatsumi K, Inami T, Ikeda N, Taniguchi Y, Minatsuki S, Murohara T, Yasuda S, Fukuda K, Tsutsui H. Efficacy and safety of edoxaban in patients with chronic thromboembolic pulmonary hypertension: protocol for a multicentre, randomised, warfarin-controlled, parallel group trial - KABUKI trial. BMJ Open. 2022 Jul 19;12(7):e061225. doi: 10.1136/bmjopen-2022-061225.
PubMed 37070473
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigator-initiated, Multicenter, Phase 3, Randomized, Single-blind, Double-dummy, Parallel-group Study of Evaluate the Efficacy and Safety of Edoxaban Versus Warfarin (Vitamin K Antagonist) in Subjects With Chronic Thromboembolic Pulmonary Hypertension Taking Warfarin (Vitamin K Antagonist) at Baseline: KABUKI
- ClinicalTrials.gov ID
- NCT04730037
- Acronym / sponsor ID
- CTR225-01
- Conditions
- CTEPH
- Keywords
- Edoxaban, DOAC, Wafrarin, Anticoagulation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Kyushu UniversityUniversity, hospital or other
- Collaborators
- Daiichi Sankyo Co., Ltd.
- Study start
- 23 Mar 2021 (actual)
- Primary completion
- 30 Mar 2023 (actual)
- Study completion
- 27 Jun 2023 (actual)
- First posted
- 29 Jan 2021 (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.
This is phase III trial to evaluate whether edoxaban, a direct factor Xa inhibitor, is noninferior to warfarin in preventing worsening of chronic thromboembolic pulmonary hypertension (CTEPH).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Edoxaban group | Active comparator | Drug: Edoxaban, Drug: Warfarin Potassium placebo |
| Warfarin group | Active comparator | Drug: Warfarin Potassium, Drug: Edoxaban placebo |
Who may qualify
- Ages
- 20 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient who once* diagnosed with CTEPH based on at least 2 imaging study (VQ scan, CT pulmonary angiogram, or catheter-based pulmonary angiogram) and hemodynamic criteria (MPAP >=25 mmHg and PAWP =< 15 mmHg). *Patients treated with PEA, BPA, or vasodilators, who do not meet hemodynamic criteria at the registration, are eligible.
- Patients who are not planned to require increased / changed / discontinuation of PEA, BPA, or pulmonary vasodilators within 12months
- Stable administration of vitamin K antagonists
- WHO functional class I-III
- Patients who meet A) B)and C) by 90 days prior to baseline. A)No addition, reduction, or change of endothelin antagonists, soluble guanylate cyclase stimulants, phosphodiesterase-5 inhibitors, prostacyclin, and its derivatives, or calcium antagonists. B)Appropriate anticoagulants have been continued. C)No BPA has been done.
Key exclusion criteria (15 listed)
- Patients with severe lung disease (FEV1.0/FVC < 60% or %TLC < 60%)
- Patients with acute or chronic disabilities that interfere with clinical trial requirements
- Patients with acute symptomatic PE within 180 days prior to the start of study drug administration
- Patients with congenital heart disease who have not undergone radical surgery
- Patients who cannot provide informed consent due to mental disorders, dementia, or other illnesses
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 |
|---|---|---|
| Edoxaban- Edoxaban 30 mg/60 mg tablet according to body weight. 60 kg or less: 30 mg once daily, over 60 kg: 60 mg once daily, reduced to 30 mg once daily depending on renal function and concomitant medications | Drug | Edoxaban group |
| Warfarin Potassium- Warfarin K 1 mg tablets once daily (Dose adjusted with target PT-INR of 1.5-2.5) | Drug | Warfarin group |
| Warfarin Potassium placebo- Warfarin K 1 mg placebo tablets once daily | Drug | Edoxaban group |
| Edoxaban placebo- Edoxaban 30 mg/60 mg placebo tablet according to body weight. 60 kg or less: 30 mg once daily, over 60 kg: 60 mg once daily, reduced to 30 mg once daily depending on renal function and concomitant medications | Drug | Warfarin group |
Primary outcome
Ratio of 1-year resting PVR to baseline resting PVR
Time frame: Week 48 of treatment
5 secondary outcomes
Percentage of cases with worsening of CTEPH
Time frame: Throughout the study duration(up to week48)
Change from baseline in 6-minute walk distance
Time frame: Week16, 32, 48 of treatment
Change from baseline in WHO functional class
Time frame: Week16, 32, 48 of treatment
Change from baseline in NT-proBNP
Time frame: Week16, 32, 48 of treatment
Percentage of cases with clinically relavant bleeding (ISTH 2015 definition)
Time frame: Throughout the study duration(up to week48)
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 5 Oct 2023.
- Background: PubMed 31200342Hosokawa K, Abe K, Tsutsui H. Use of direct oral anticoagulants prevents increase in pulmonary vascular resistance and incidence of clinical worsening in patients with chronic thromboembolic pulmonary hypertension. Thromb Res. 2019 Aug;180:43-46. doi: 10.1016/j.thromres.2019.05.018. Epub 2019 May 31. No abstract available.
- Derived from this study: PubMed 37070473Hosokawa K, Abe K, Kishimoto J, Kobayakawa Y, Todaka K, Tamura Y, Tatsumi K, Inami T, Ikeda N, Taniguchi Y, Minatsuki S, Murohara T, Yasuda S, Fukuda K, Tsutsui H. Efficacy and safety of edoxaban in patients with chronic thromboembolic pulmonary hypertension: protocol for a multicentre, randomised, warfarin-controlled, parallel group trial - KABUKI trial. BMJ Open. 2022 Jul 19;12(7):e061225. doi: 10.1136/bmjopen-2022-061225.
- Individual participant dataSharing planned: No. Data are available upon reasonable request. The deidentified participant data collected in this study will be shared with manufacturers of investigational drugs, Ministry of Health, Labor and Welfare, and regulatory authorities related to pharmaceutical affairs. Data are attributed to Kyushu University and Daiichi Sankyo Co., Ltd. Protocols, informed consent form, and statistical analysis plans will be shared upon reasonable request. Contact: abe.kotaro.232@m.kyushu-u.ac.jp
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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.
Kohtaro Abe principal investigator
Kyushu University Hospital
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 Edoxaban and Warfarin Potassium in people with CTEPH, run by Kyushu University at 1 site in Japan.
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 7 inclusion and 15 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 5 Oct 2023. 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 Japan. 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?
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?
Ratio of 1-year resting PVR to baseline resting PVR (time frame: Week 48 of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04730037, which also lists 2 linked publications.
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 5 Oct 2023.