Effects of Elobixibat in patients with heart failure complicated with chronic constipation

JRCT ID: jRCTs071190055

Registered date:27/03/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Heart failure complicated with chronic constipation
• Date of first enrollment: 17/08/2020
• Target sample size: 50
• Study type: Interventional
• Intervention(s): To instruct taking Elobixibat 5mg 2 tablets orally once a day before meals. The administration period is 12 weeks. Start taking Elobikibat 10mg per day before meals after returning the ABPM at Visit2 or Visit 3 (on the day or next day), and continue taking Erobikibat until Visit 7 by the ABPM should be returned. The maximum dose is 15 mg per day according to the package insert though it may be adjusted or administration should be discontinued according to the symptoms.

Outcome(s)

Primary Outcome

Comparison of weekly frequency* of spontaneous bowel movement between pre-treatment period and week 12 of administration
*Frequency of bowel movement without suppositories, enema or disimpaction during the 7 days before each visit

Secondary Outcome

1.Endpoints for constipation
1) Changes in the frequency and transition of spontaneous bowel movement from pre-treatment to week 4 or week 8 of administration
2) Changes and transitions in the degree of straining during defecation from pre-treatment to week 4, week 8 or week 12 of administration
3) Changes in BSFS from pre-treatment to week 12 of administration
4) Changes and transitions in complete spontaneous bowel movement* from pre-treatment to week 4, week 8 or week 12 of administration
5) Subpopulation analysis by background factor of patients and administration dose of study drug
* Bowel movement without a sense of remaining stool without use of intestinal laxative, enema or digital evacuation
2. Endpoints for cardiac and renal function
1) Changes and transitions in the concentration of blood BNP, PRA, and ALD from pre-treatment to week 4, week 8, or week 12 of administration
2) Comparison of the blood pressure measured by ABPM between pre-treatment and week 12 of administration
3) Changes and transitions in the concentration of blood lipid (LDL-C, HDL-C, TG, T-Cho) from pre-treatment to week 4, week 8 or week 12 of administration
4) Changes and transitions in body weight from pre-treatment to week 4, week 8, or week 12 of administration
5) Changes and transitions in eGFR from pre-treatment to week 4, week 8, or week 12 of administration
6) Subpopulation analysis by background factor and endpoint for constipation
3. Endpoints for safety
1) Incidence rate of adverse events and adverse reactions
2) Rate of dropped out patient and discontinued administration of study drug

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients with chronic constipation who meet every those following criteria
(At the time of registration(enrollment))
1.Patients with chronic constipation who meet every those following criteria
1) Meet 2 or more of the following six items
a. Straining during more than one-fourth (25%) of defections
b. Lumpy or hard stools (BSFS 1-2) more than one-fourth (25%) of defections
c. Sensation of incomplete evacuation more than one-fourth (25%) of defections
d. Sensation of anorectal obstruction/blockage more than one-fourth (25%) of defections
e. Manual maneuvers to facilitate more than one-fourth (25%) of defections (eg, digital evacuation, support of the pelvic floor)
f. Fewer than 3 spontaneous bowel movement per week
2) Meet every those following 3 items
a. Rare to have loose stools without using laxtive
b. Never been given diagnosis as irriable bowel syndrome
c. Symptoms have been oresent since more than 6 months and meet the criteria 1.-1) for last 3 months..
2.Outpatients with stable heart failure who meet every those following criteria
1) Classification of NYHA cardiac function is belong to II or III.
2) No change in any prescription for heart failure within 12 weeks before obtaining Informed Consent
3) No hospitalization history for heart disease treatment within 6 months before obtaining Informed Consent
4) Patients judged by doctors to be able to observe during the pre-observation and administration period
3.Male and female over 20 years old at the date of Informed Consent
4.Patients who are given sufficient description about participation in this study and sufficiently understand it, providing their consent in document by their own free will
5.Patients who can write a defecation diary during the study period

Exclude criteria

Patients who is applicable those followings to be excluded
(At the time of registration(enrollment), at theVisit 2)
1.Patients with a history of hypersensitivity to Elobixibat
2.Patients with confirmed or suspected bowel obstruction due to tumor, hernia, etc.
3.Patients with severe hepatopathy (AST or ALT is 3 times or more for upper limit of in-hospital standard.)
4.Patients to be suspected of having biliary atresia or a reducing secretion of bile acid
5.Patients suspected of organic constipation
6.Female patients who are pregnant, breastfeeding, or hope to raise children
7.Patients who are taking bile acid preparations (ursodeoxycholic acid, chenodeoxycholic acid), aluminum-containing preparations (sucralfate hydrate, aldioxa, etc.), cholestyramine, colestimide or midazolam
8.Patients who are judged to be ineligible for this research by investigator because of threatening the safety or poor protocol compliance
(At the Visit 2)
9.Patients who have taken Elobixibat during the previous observation period

Related Information

• Primary Sponsor: Tsujita Kenichi
• Secondary Sponsor: EA Pharma Co., Ltd.,MOCHIDA PHARMACEUTICAL CO., LTD.