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

NCT04730037 | Completed Phase 3 DMC

• 1 other identifier: CTR225-01
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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).

Conditions

CTEPH

Keywords

Edoxaban; DOAC; Wafrarin; Anticoagulation

Outcome Measures

Primary Outcomes (1)

• Ratio of 1-year resting PVR to baseline resting PVR

  Week 48 of treatment

Secondary Outcomes (5)

• Percentage of cases with worsening of CTEPH

  Throughout the study duration(up to week48)

• Change from baseline in 6-minute walk distance

  Week16, 32, 48 of treatment

• Change from baseline in WHO functional class

  Week16, 32, 48 of treatment

• Change from baseline in NT-proBNP

  Week16, 32, 48 of treatment

• Percentage of cases with clinically relavant bleeding (ISTH 2015 definition)

  Throughout the study duration(up to week48)

Study Arms (2)

Edoxaban group

ACTIVE COMPARATOR

Drug: Edoxaban; Drug: Warfarin Potassium placebo

Warfarin group

ACTIVE COMPARATOR

Drug: Warfarin Potassium; Drug: Edoxaban placebo

Interventions

Edoxaban DRUG

\- 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

Edoxaban group

Warfarin Potassium DRUG

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

Warfarin group

Warfarin Potassium placebo DRUG

\- Warfarin K 1 mg placebo tablets once daily

Edoxaban group

Edoxaban placebo DRUG

\- 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

Warfarin group

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kyushu University: lead
• Daiichi Sankyo Co., Ltd.: collaborator

Study Sites (1)

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Related Publications (2)

• 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.

  PMID: 31200342 BACKGROUND

• Hosokawa 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.

  PMID: 37070473 DERIVED

MeSH Terms

Interventions

edoxaban; Warfarin

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Kohtaro Abe

  Kyushu University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Cardiovascular Medicine, Faculty of Medical Sciences

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: January 29, 2021
• Study Start: March 23, 2021
• Primary Completion: March 30, 2023
• Study Completion: June 27, 2023
• Last Updated: October 5, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)