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

CTEPH Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04730037
• Other study ID #: CTR225-01
• Status: Completed
• Phase: Phase 3
• Start date: March 23, 2021
• Est. completion date: June 27, 2023

Study information

• Verified date: October 2023
• Source: Kyushu University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: June 27, 2023
• Est. primary completion date: March 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• CTEPH

Intervention

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

Locations

Country	Name	City	State
Japan	Kyushu University Hospital	Fukuoka

Sponsors (2)

Lead Sponsor	Collaborator
Kyushu University	Daiichi Sankyo Co., Ltd.

Country where clinical trial is conducted

Japan, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ratio of 1-year resting PVR to baseline resting PVR		Week 48 of treatment
Secondary	Percentage of cases with worsening of CTEPH		Throughout the study duration(up to week48)
Secondary	Change from baseline in 6-minute walk distance		Week16, 32, 48 of treatment
Secondary	Change from baseline in WHO functional class		Week16, 32, 48 of treatment
Secondary	Change from baseline in NT-proBNP		Week16, 32, 48 of treatment
Secondary	Percentage of cases with clinically relavant bleeding (ISTH 2015 definition)		Throughout the study duration(up to week48)