Clinical trial NCT04730037: Clinical Trial to Investigate Safety and Efficacy of Edoxaban in Patients With CTEPH (KABUKI)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: CTEPH
Keywords: Edoxaban
DOAC
Wafrarin
Anticoagulation
Lead sponsor: Kyushu University
Sponsor class: OTHER
Collaborators: name: Daiichi Sankyo Co., Ltd.
First posted: 2021-01-29
Enrollment: 74
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: Inclusion Criteria:

1. 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.
2. Patients who are not planned to require increased / changed / discontinuation of PEA, BPA, or pulmonary vasodilators within 12months
3. Stable administration of vitamin K antagonists
4. WHO functional class I-III
5. 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.
6. Patients who have not undergone PEA from 180 days prior to baseline right heart catheterization to the start date of study drug administration
7. Patients with a 6-minute walking distance \>=150m

Exclusion Criteria:

1. Patients with severe lung disease (FEV1.0/FVC \< 60% or %TLC \< 60%)
2. Patients with acute or chronic disabilities that interfere with clinical trial requirements
3. Patients with acute symptomatic PE within 180 days prior to the start of study drug administration
4. Patients with congenital heart disease who have not undergone radical surgery
5. Patients who cannot provide informed consent due to mental disorders, dementia, or other illnesses
6. Patients with advanced cancer
7. Patients with a life expectancy of less than 1 year
8. Patients with active hemorrhagic lesions
9. Patients with comorbidities requiring vitamin K antagonist
10. Patients receiving other study drug within 30 days prior to randomization
11. Patients with renal dysfunction (Ccr 15 mL/min)
12. Patients with liver dysfunction (Child-Pugh B or C)
13. Females of reproductive age not using an acceptable form of contraception/Pregnant/Breastfeeding
14. Patients contraindicated for edoxaban or warfarin
15. Patients with hypersensitivity to any of the drug

Primary outcomes:
measure: Ratio of 1-year resting PVR to baseline resting PVR
timeFrame: Week 48 of treatment
Secondary outcomes:
measure: Percentage of cases with worsening of CTEPH
timeFrame: Throughout the study duration(up to week48)
measure: Change from baseline in 6-minute walk distance
timeFrame: Week16, 32, 48 of treatment
measure: Change from baseline in WHO functional class
timeFrame: Week16, 32, 48 of treatment
measure: Change from baseline in NT-proBNP
timeFrame: Week16, 32, 48 of treatment
measure: Percentage of cases with clinically relavant bleeding (ISTH 2015 definition)
timeFrame: Throughout the study duration(up to week48)
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
Study officials:
affiliation: Kyushu University Hospital
name: Kohtaro Abe
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.