UMIN-CTR Clinical Trial

Public title

An Observational Study on the Effect of Antimicrobial Stewardship Program in ICU

Acronym

An Observational Study on the Effect of Antimicrobial Stewardship Program in ICU

Scientific Title

An Observational Study on the Effect of Antimicrobial Stewardship Program in ICU

Scientific Title:Acronym

An Observational Study on the Effect of Antimicrobial Stewardship Program in ICU

Region

Japan

Condition

Infectious disease

Classification by specialty

Infectious disease

Intensive care medicine

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

We will analyze 1) the use of antimicrobial drugs, 2) the pattern of antimicrobial resistant bacteria and 3) the prognosis of patients who received antimicrobial drugs prior to and after the inception of Antibiotic Stewardship Program.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Primary outcomes

Patient outcomes 30 days after discharge from ICU

Key secondary outcomes

Patient outcome at the time of discharge from ICU, Antimicrobial Use Density (AUD), Days Of Therapy (DOT), the pattern of antimicrobial resistant bacteria and antimicrobial de-escalation rate.

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

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

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patients admitted to the ICU

Key exclusion criteria

Patients who refuse to participate in the study

Target sample size

6000

Name of lead principal investigator

1st name	Hidenobu
Middle name
Last name	Shigemitsu

Organization

Tokyo Medical and Dental University, Medical hospital

Division name

Department of Intensive Care Medicine

Zip code

113-8519

Address

1-5-45 Yushima Bunkyo-ku Tokyo

TEL

03-5803-5652

Email

hshiccm@tmd.ac.jp

Name of contact person

1st name	Yuka
Middle name
Last name	Mishima

Organization

Tokyo Medical and Dental University, Medical hospital

Division name

Department of Intensive Care Medicine

Zip code

113-8519

Address

1-5-45 Yushima Bunkyo-ku Tokyo

TEL

03-5803-5652

Homepage URL

Email

ykmishima.icu@tmd.ac.jp

Institute

Department of Intensive Care Medicine, Tokyo Medical and Dental University

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Research Ethics Committee, Tokyo Medical and Dental University

Address

1-5-45 Yushima Bunkyo-ku Tokyo

Tel

03-3813-6111

Email

syomu1.adm@tmd.ac.jp

Secondary IDs

YES

Study ID_1

M2019-055

Org. issuing International ID_1

Research Ethics Committee, Tokyo Medical and Dental University

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

東京医科歯科大学医学部附属病院（東京都）

Date of disclosure of the study information

2019

Year

11

Month

30

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

https://journals.lww.com/ccejournal/Fulltext/2023/01000/Impact_of_Antibiotic_Time_Outs_in.9.aspx

Number of participants that the trial has enrolled

1573

Results

Implementation of antimicrobial time-outs (ATO) during the multidisciplinary rounds in the ICU improved the subdistribution hazard ratio for survival discharge as 1.13 [95% confidence interval: 1.02, 1.25], suggesting a reduction in length of hospital stay among patients.
The day of therapy (DOT) for IV antibiotics in the ICU decreased significantly after the implementation of ATO (interrupted time-series analysis: intercept -178.26 [95% CI: -317.74, -38.78], slope -7.00 [95% CI: -15.77, 1.78]).

Results date posted

2023

Year

01

Month

30

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The number of patients before ATO implementation (Phase 1) was 777 and after ATO implementation (Phase 2) was 796. Patients of scheduled ICU admissions were Phase 1 vs. Phase 2: 68.1% vs. 70.6%. Operation patients were 75.8% vs. 80.0%. Patients with infection as primary reason for ICU admission were 9.7% vs. 8.9%.

Participant flow

This study was conducted between October 2016 and March 2020.Pre-ATO period was October2016 to May 2018, and ATO period was June 2018 to March 2020. The last one year of pre-ATO period (June 2017 to May 2018) was Phase 1, and the last one year of ATO period (April 2019 to March 2020) was Phase 2. All patients aged 16 years and older were included. We excluded patients who had been hospitalized for greater than 2 years, whose hospitalization overlapped these two phases, and those who were readmitted to the ICU after their initial ICU admission.

Adverse events

Outcome measures

Survival to hospital discharge and ICU discharge were compared between Phase 1 and Phase 2 with the Fine-Gray model, and the subdistribution hazard ratios (SHRs) was calculated. The changes in DOT were evaluated using an interrupted time-series analysis with linear regression analysis. We examined the changes in DOT immediately after ATO was introduced (determined by changes in the intercept), and the consistency of the change over the period of the intervention (determined by the slope following the ATO introduction).

Primary outcome: SHR for survival to hospital discharge 1.13 [95% CI: 1.02, 1.25] (p = 0.02)
Secondary outcome: SHR for survivla to ICU discharge 0.94 [95%CI: 0.87, 1.02] (p = 0.11)
DOT of total IV antiviotics: slope in the pre-ATO period -7.45 [95% CI: 15.95, 1.04] (p = 0.09), change in intercept -178.26 [95% CI: -317.74, -38.78] (p = 0.02), change in slope -7.00 [95% CI: -15.77, 1.78] (p = 0.13)
DOT of antipseudomonal antibiotics: slope in the pre-ATO period 0.43 [95% CI: -2.84, 3.71] (p = 0.80), change in intercept -65.06 [95% CI: -118.31, -11.82] (p = 0.02), change in slope -4.51 [95% CI: -7.64, -1.39] (p < 0.01)
DOT of carbapenem: slope in the pre-ATO period -3.89 [95% CI: -6.36, -1.43] (p < 0.01), change in intercept 9.29 [95% CI: -31.18, 49.76] (p = 0.66), change in slope -2.98 [95% CI: -5.38, -0.58] (p = 0.02)
DOT of anti-MRSA antibiotics: slope in the pre-ATO period -0.25 [95% CI: -2.75, 2.26] (p = 0.85), change in intercept -88.86 [95% CI: -129.34, -48.39] (p < 0.01), cange in slope -3.28 [95% CI: -5.90, -0.66] (p = 0.02)

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2019

Year

10

Month

15

Day

Date of IRB

2020

Year

01

Month

30

Day

Anticipated trial start date

2020

Year

01

Month

30

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

Design: Before-After Study.
Participants: All ICU patients on the survey period.
Survey Period:
(1) Before launching Antimicrobial Stewardship Program: from April 2015 to September 2016.
(2) After launching Multidisciplinary Rounds in ICU: from October 2016 to May 2018.
(3) After launching "Time out": from June 2018 to March 2021.

Registered date

2019

Year

11

Month

19

Day

Last modified on

2023

Year

01

Month

30

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043394