CTEPH
Conditions
Keywords
Edoxaban, DOAC, Wafrarin, Anticoagulation
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).
Interventions
DRUGEdoxaban
\- 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 K 1 mg tablets once daily (Dose adjusted with target PT-INR of 1.5-2.5)
DRUGWarfarin Potassium placebo
\- Warfarin K 1 mg placebo tablets once daily
DRUGEdoxaban 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
Sponsors
Daiichi Sankyo Co., Ltd.
Kyushu University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
20 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ratio of 1-year resting PVR to baseline resting PVR | Week 48 of treatment |
Secondary
| Measure | Time frame |
|---|---|
| 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) |
| 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 |
Countries
Japan
Outcome results
None listed