Phase III Investigator-Initiated Trial to Investigate Safety and Efficacy of Edoxaban in Patients with Chronic Thromboembolic Pulmonary Hypertension

JRCT ID: jRCT2071200098

Registered date:08/02/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Chronic Thromboembolic Pulmonary Hypertension
• Date of first enrollment: 09/04/2021
• Target sample size: 74
• Study type: Interventional

Intervention(s)

Oral administeration of (1) or (2)
(1) Edoxaban group
- 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 placebo tablets once daily

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

Outcome(s)

• Primary Outcome: Ratio of 1-year resting PVR to baseline resting PVR

Secondary Outcome

Efficacy
1)Percentage of cases with CTEPH exacerbation events
2)Change from baseline in distance of 6-minute walking test (Visit 5, 7, 9)
3)Change from baseline in WHO functional classification class (Visit 5, 7, 9)
4)Change from baseline in NT-proBNP concentration (Visit 5, 7, 9)

Safety
Percentage of cases with clinically significant bleeding

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

1)Male and female patients >= 20 or =< 85 years of age
2)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.
3)Patients who are not planned to require increased / changed / discontinuation of PEA, BPA, or pulmonary vasodilators within 12 months
4)Stable administration of vitamin K antagonists
5)WHO functional class I-III
6)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, prostacyclin agonist, or calcium antagonists
B)Appropriate anticoagulants have been continued
C)No BPA has been done
7)Patients who have not undergone PEA from 180 days prior to baseline right heart catheterization to the start date of study drug administration
8)Patients with a 6-minute walking distance >=150m

Exclude 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 additives
16)Patients judged unsuitable by investigators

Related Information

• Primary Sponsor: Abe Kohtaro
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development (AMED),Daiichi-Sankyo Co.,Ltd.