UMIN-CTR Clinical Trial

Public title

CPAP Effects on Atherosclerotic Plaques in Patients with Sleep-Disordered Breathing and Coronary Artery Disease

Acronym

The ENTERPRISE trial

Scientific Title

CPAP Effects on Atherosclerotic Plaques in Patients with Sleep-Disordered Breathing and Coronary Artery Disease

Scientific Title:Acronym

The ENTERPRISE trial

Region

Japan

Condition

Patients with stable coronary artery disease and sleep-disordered breathing

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate the effects of adding CPAP treatment to optimal medical treatment on coronary plaque in patients with sleep-disordered breathing and coronary artery disease.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Percentage changes in plaque atheroma volume in the non-culprit lesion measured by IVUS from baseline to 12 months

Key secondary outcomes

(1) Absolute changes in maxLCBI4mm and maxLCBI10mm in the non-culprit lesion segment by NIRS analysis from baseline to 12 months
(2) Absolute change in total atheroma volume in the non-culprit lesion measured by IVUS from baseline to 12 months
(3) Absolute change in serum high-sensitivity C-reactive protein level from baseline to 12 months
(4) Major adverse cardiac and cerebrovascular events, defined as composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina, target vessel revascularization including target lesion revascularization and non-target lesion target vessel revascularization and hospitalization for congestive heart failure, and all-cause death during the follow-up period.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

No treatment

Stratification

Dynamic allocation

YES

Institution consideration

Blocking

YES

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Device,equipment

Interventions/Control_1

Continuous positive airway pressure (CPAP) for 12 months

Interventions/Control_2

no-CPAP for 12 months

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

20

years-old

<=

Age-upper limit

75

years-old

>

Gender

Male and Female

Key inclusion criteria

1. Patients who have been diagnosed with stable coronary heart disease
2. Patients with 3%ODI >15 events/h
3. Successful PCI for significant coronary stenotic lesion under IVUS guidance
4. Patients having non-calcified plaque with maximal plaque burden > 40% of the non-culprit lesion segment detected by IVUS
5. Patients who agree to be enrolled in the trial, providing signed written informed consent

Key exclusion criteria

1. Patients treated with CPAP therapy
2. Patients with hypersomnia requiring urgent treatment (defined as an Epworth Sleepiness Scale [ESS] score >18)
3. Patients over 75 years of age
4. Patients with New York Heart Association class II, III, or IV heart failure
5. Patients with renal insufficiency (serum creatinine 2.0 mg/dL)
6. Patients with hemodialysis
7. Patients with malignant disease
8. Patients recognized as inadequate by attending physician

Target sample size

100

Name of lead principal investigator

1st name	Tomotaka
Middle name
Last name	Dohi

Organization

Juntendo University School of Medicine

Division name

Department of Cardiovascular Medicine

Zip code

113-8421

Address

3-1-3 Hongo, Bunkyo-ku, Tokyo, Japan

TEL

03-3813-3111

Email

tdohi@juntendo.ac.jp

Name of contact person

1st name	Tomotaka
Middle name
Last name	Dohi

Organization

Juntendo University School of Medicine

Division name

Department of Cardiovascular Medicine

Zip code

113-8421

Address

3-1-3 Hongo, Bunkyo-ku, Tokyo, Japan

TEL

03-3813-3111

Homepage URL

Email

tdohi@juntendo.ac.jp

Institute

Department of Cardiovascular Medicine, Juntendo University School of Medicine, Tokyo, Japan

Institute

Department

Personal name

Organization

Teijin Pharma Limited

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Juntendo University Hospital

Address

3-1-3 Hongo, Bunkyo-ku, Tokyo, Japan

Tel

03-5802-1584

Email

kenkyu5858@juntendo.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2018

Year

07

Month

01

Day

URL releasing protocol

https://www.journal-of-cardiology.com/article/S0914-5087%2818%2930219-3/fulltext

Publication of results

Unpublished

URL related to results and publications

Submitted

Number of participants that the trial has enrolled

47

Results

Finally, the CPAP group (n=23) and non-CPAP group (n=24) were analyzed. Compared to the non-CPAP group, the CPAP group had a significantly decreased percentage atheroma volume (adjusted difference -2.81+/-1.10%, p=0.014) by analysis of covariance, and tended to have a lower incidence rate of MACCE, mainly driven by a decrease in target vessel revascularization (4% vs. 25%, p=0.097).

Results date posted

2024

Year

01

Month

03

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The mean patient age was 62+/-8 years, and 96% of them were males. The prevalence of hypertension, diabetes mellitus, current smoking, family history of premature coronary artery disease, chronic kidney disease, and history of myocardial infarction were 94%, 64%, 21%, 13%, 19%, and 40%, respectively. The baseline clinical characteristics, including laboratory data, echographic data, medications and sleep parameters were similar between the CPAP group and non-CPAP groups.

Participant flow

53 patients with stable coronary artery disease who underwent PCI using NIRS-IVUS, coexisting with SDB was defined as a 3% oxygen desaturation index 15 events/hour or higher using pulse oximeter were recruited. The randomization was stratified using permuted blocked randomization,　according to the two stratification factors, as follows: body mass index less than 25 kg/m2 or 25 kg/m2 or higher and 3% oxygen desaturation index less than 30 events/hour or 30 events/hour or higher. Three patients in the CPAP group and three in the non-CPAP group discontinued during the follow-up period; therefore, 47 patients completed the study and were analyzed.

Adverse events

One patient felt dyspnea due to CPAP, and one patient developed gastric ulcer but no clear causal relationship with CPAP was observed.

Outcome measures

Compared to the non-CPAP group, the CPAP group had a significantly decreased percentage atheroma volume (adjusted difference -2.81+/-1.10%, p=0.014) by analysis of covariance, and tended to have a lower incidence rate of MACCE, mainly driven by a decrease in target vessel revascularization (4% vs. 25%, p=0.097). However, there was no significant difference in absolute change in maxLCBI4mm (0 [-32, 40] vs. 34 [-71, 163], p=0.312), absolute change in total atheroma volume (-4 [-30, 1] vs. -3 [-13, 8], p=0.170), and absolute change in serum high-sensitivity C-reactive protein levels between the two groups analyzed by Mann-Whitney U test, and no all-cause death was observed.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2018

Year

06

Month

01

Day

Date of IRB

2018

Year

07

Month

01

Day

Anticipated trial start date

2018

Year

07

Month

01

Day

Last follow-up date

2022

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

06

Month

07

Day

Last modified on

2024

Year

01

Month

03

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000036293