Clinical Trial to Investigate Safety and Efficacy of Edoxaban in Patients With CTEPH (KABUKI)

Sponsor

Kyushu University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04730037

Collaborator

Daiichi Sankyo Co., Ltd. (Industry)

Enrollment

Location

Arms

26.7

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
CTEPH	Drug: Edoxaban Drug: Warfarin Potassium Drug: Warfarin Potassium placebo Drug: Edoxaban placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

74 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 9, 2021

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Edoxaban group	Drug: 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: Warfarin Potassium placebo - Warfarin K 1 mg placebo tablets once daily
Active Comparator: Warfarin group	Drug: Warfarin Potassium - Warfarin K 1 mg tablets once daily (Dose adjusted with target PT-INR of 1.5-2.5) Drug: 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

Arm

Intervention/Treatment

Active Comparator: Edoxaban group

Drug: 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: Warfarin Potassium placebo

- Warfarin K 1 mg placebo tablets once daily

Active Comparator: Warfarin group

Drug: Warfarin Potassium

- Warfarin K 1 mg tablets once daily (Dose adjusted with target PT-INR of 1.5-2.5)

Drug: 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

Outcome Measures

Primary Outcome Measures

Ratio of 1-year resting PVR to baseline resting PVR [Week 48 of treatment]

Secondary Outcome Measures

Percentage of cases with CTEPH exacerbation events [Throughout the study duration(up to week48)]
Change from baseline in distance of 6-minute walking test [Week16, 32, 48 of treatment]
Change from baseline in WHO functional classification class [Week16, 32, 48 of treatment]
Change from baseline in NT-proBNP concentration [Week16, 32, 48 of treatment]
Percentage of cases with clinically significant bleeding [Throughout the study duration(up to week48)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient who once* diagnosed with CTEPH based on imaging study (VQ scan, CT 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

Exclusion Criteria:

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
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