UMIN-CTR Clinical Trial

Public title

Surveys on Medication Adherence of Anticoagulant Drugs and Investigation for Improvement of Medication Adherence by Educational Program in Non-Valvular Atrial Fibrillation Patients

Acronym

SMAAP-AF study

Scientific Title

Surveys on Medication Adherence of Anticoagulant Drugs and Investigation for Improvement of Medication Adherence by Educational Program in Non-Valvular Atrial Fibrillation Patients

Scientific Title:Acronym

SMAAP-AF study

Region

Japan

Condition

Non-valvular atrial fibrillation

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To measure medication adherence to edoxaban (once daily) or apixaban (twice daily) in non-valvular atrial fibrillation (NVAF) patients taking direct oral anticoagulants (DOAC) and to examine the effect of educational intervention on medication adherence.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Adherence difference estimated by the electronic monitoring device between the observation and intervention periods (each period for 12 weeks)

Key secondary outcomes

Adherence estimated by the electronic monitoring device during the observation p3riod (12 weeks)

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Single blind -participants are blinded

Control

Active

Stratification

Dynamic allocation

YES

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Educational,Counseling,Training

Type of intervention

Other

Interventions/Control_1

Educational Program for the DOAC use

Interventions/Control_2

Regular medication instruction

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1 NVAF patients in outpatient clinics
2 Patients taking edoxaban or apixaban for more than 4 weeks prior to enrolling in this trial
3 In participating in this study, patients who received written consent

Key exclusion criteria

1 Patients participating in or participating in other clinical trials
2 Patients who are considered difficult to examine medication adherence
3 Patients requiring family member or others supports with medication management
4 Inpatients
5 Patients were pregnant or expecting to become pregnant within the duration of the study
6 Patients judged unsuitable as research subjects by the investigators

Target sample size

400

Name of lead principal investigator

1st name	Nobuhisa
Middle name
Last name	Hagiwara

Organization

Tokyo Women's Medical University

Division name

Cardiology

Zip code

162-8666

Address

8-1 Kawada-cho, Shinjuku-ku, Tokyo

TEL

03-3353-8111

Email

hagiwara.nobuhisa@twmu.ac.jp

Name of contact person

1st name	Tsuyoshi
Middle name
Last name	Shiga

Organization

Tokyo Women's Medical University

Division name

Cardiology

Zip code

162-8666

Address

8-1 Kawada-cho, Shinjuku-ku, Tokyo

TEL

03-3353-8111

Homepage URL

Email

shiga.tsuyoshi@twmu.ac.jp

Institute

Tokyo Women's Medical University

Institute

Department

Personal name

Organization

Daiichi-Sankyo

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Tokyo Women's Medical University Yachiyo Medical Center
National Hospital Organization Yokohama Medical Center

Name of secondary funder(s)

Organization

Certified Review Board, Hattori Clinic

Address

1-15-18 Bessho, Hachioji, Tokyo,JAPAN, Tokyo

Tel

03-5919-2052

Email

reception-office@hattori-irb.com

Secondary IDs

YES

Study ID_1

jRCTs031180142

Org. issuing International ID_1

Japan Registry of Clinical Trials

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

東京女子医科大学病院（東京都）
東京女子医科大学八千代医療センター（千葉県）
国立病院機構横浜医療センター（神奈川県）

Date of disclosure of the study information

2018

Year

02

Month

05

Day

URL releasing protocol

https://onlinelibrary.wiley.com/doi/10.1002/joa3.12532

Publication of results

Published

URL related to results and publications

https://doi.org/10.1016/j.clinthera.2022.09.011

Number of participants that the trial has enrolled

301

Results

The difference in the primary end point between the educational interventional program group and the standard medication counseling group was not significant (mean [SD], 2.9% [7.5%] vs 3.4% [8.3%]). On multiple linear regression analysis, the difference in DOAC adherence between the two groups was not significant, but that adherence to apixaban was significantly improved among men in the educational interventional program (beta=0.219, P=0.012).

Results date posted

2023

Year

08

Month

10

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

There was no significant difference in age (mean 73 years), gender (male 62%), CHADS2 score (mean 2), MMSE score (=<23:0), living status or work status between the groups.

Participant flow

Of the 301 patients were enrolled in the trial, 268 patients who completed Stage 1 were randomly assigned to receive either the educational program or standard medication counseling. Reasons of the withdrawal during Stage 1(observation period): 2 withdrew consent, 2 died, 4 switched to other oral anticoagulants, 9 discontinued study participation due to hospital admission, transfer to other hospital, or mental health problems, and 16 incomplete electronic records.

Adverse events

Two patients died of causes considered unrelated to treatment(sudden death, non-cardiovascular death). Hospitalization: 1 heart failure, 6 catheter ablation for AF, 1 pacemaker implantation, 1 hyperparathyroidism, 1 urinary tract infection, 1 cataract surgery, 1 colonic polypectomy and 2 malignancies. No stroke/systemic embolism or major bleeding events were observed.

Outcome measures

The primary outcome was the change in the rate of adherence to DOACs from Stage 1 to Stage 2 in patients who received the educational interventional program in Stage 2 and those who did not receive it. Medication adherence was defined as the number of days of adherence, which was the number of days on which the tablets in the PTP were accessed once every 24 hours for edoxaban or twice daily (one tablet every 12 hours) for apixaban. The medication adherence rate was the number of days that patients appropriately took the drug divided by the total number of days that the drug was prescribed as assessed by an electronic monitoring device. The secondary outcomes were safety outcomes, including major bleeding, stroke/systemic embolism, other serious adverse events, and adverse events associated with the discontinuation of the study intervention. The effect of the educational interventional program on the primary outcome was also analyzed in subgroups stratified by gender and type of DOAC.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

12

Month

22

Day

Date of IRB

2018

Year

02

Month

06

Day

Anticipated trial start date

2018

Year

05

Month

15

Day

Last follow-up date

2019

Year

05

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

02

Month

04

Day

Last modified on

2023

Year

08

Month

10

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035564