Trial Outcomes & Findings for INSPIRE Trial for Skin and Soft Tissue Infections (NCT NCT05423756)

Last Updated: 2025-08-26

Results Overview

Days-of-Therapy is a standardized national measure for antibacterial use in hospitals that counts each different antibiotic administered on each calendar day as one day of therapy, regardless of doses given. Extended-spectrum days-of-therapy per empiric day is defined as the summed number of different extended-spectrum antibiotics received per patient each calendar day, beginning at admission. If an admission is less than 3 days, only the number of days the patient is admitted will contribute to the numerator and denominator. For example, 2 different extended-spectrum antibiotics administered at least once during each of the first 3 days would yield 6 days of extended-spectrum days-of-therapy.

Recruitment status

COMPLETED

Study phase

Target enrollment

118562 participants

Primary outcome timeframe

First 3 calendar days of hospitalization for each patient during the 12-month baseline and 12-month intervention periods

Results posted on

2025-08-26

Participant Flow

92 out of 142 HCA Healthcare hospitals were recruited for this trial. There was a 12-month baseline period (January 1, 2019-December 31, 2019), 5-month phase-in (August 2, 2022-December 31, 2022), and 12-month intervention (January 1, 2023-December 31, 2023). Data from the phase-in period were excluded from all analyses (i.e., Baseline, Intervention, Outcome Measures, and Adverse Events).

118,562 patients across 92 hospitals were randomized to either the routine stewardship group (Arm 1) or to the CPOE bundle (Arm 2); 2 hospitals were excluded because they divested from HCA Healthcare before the intervention period began.

Unit of analysis: Hospitals

Participant milestones

Participant milestones
Measure	Arm 1: Routine Stewardship Continuation of routine antibiotic stewardship strategies. Arm 1: Routine Care: Routine Antibiotic Stewardship Arm - Continuation of antibiotic stewardship activities in accordance with national standards.	Arm 2: INSPIRE CPOE Bundle Use of computerized physician order entry (CPOE) smart prompts, clinician feedback, and activities to support CPOE adoption (including education and alignment of CPOE workflows) to guide empiric choice of antibiotics for skin/soft tissue infection in the first 3 days of hospitalization. Arm 2: INSPIRE Stewardship Bundle for Skin and Soft Tissue Infection: Quality improvement intervention that includes (1) computerized physician order entry (CPOE) decision support alert that provides physicians with patient-specific risk estimates for having a skin/soft tissue infection due to a multidrug-resistant organism (MDRO) and recommends standard spectrum antibiotics for low risk patients in the first 3 days of hospitalization; (2) clinician feedback reports, and (3) activities to support CPOE adoption (including education and alignment of CPOE workflows). Other antibiotic stewardship activities to continue in accordance with national standards.
Baseline (12 Months) STARTED	29595 46	28242 46
Baseline (12 Months) COMPLETED	29595 46	28242 46
Baseline (12 Months) NOT COMPLETED	0 0	0 0
Intervention (12 Months) STARTED	31337 46	29388 44
Intervention (12 Months) COMPLETED	31337 46	29388 44
Intervention (12 Months) NOT COMPLETED	0 0	0 0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: First 3 calendar days of hospitalization for each patient during the 12-month baseline and 12-month intervention periods

Population: The total number of participants analyzed reported here is from the baseline and intervention periods

Outcome measures

Outcome measures
Measure	Arm 1: Routine Stewardship n=60932 Participants Continuation of routine antibiotic stewardship strategies. Arm 1: Routine Care: Routine Antibiotic Stewardship Arm - Continuation of antibiotic stewardship activities in accordance with national standards.	Arm 2: INSPIRE CPOE Bundle n=57630 Participants Use of computerized physician order entry (CPOE) smart prompts, clinician feedback, and activities to support CPOE adoption (including education and alignment of CPOE workflows) to guide empiric choice of antibiotics for skin/soft tissue infection in the first 3 days of hospitalization. Arm 2: INSPIRE Stewardship Bundle for Skin and Soft Tissue Infection: Quality improvement intervention that includes (1) computerized physician order entry (CPOE) decision support alert that provides physicians with patient-specific risk estimates for having a skin/soft tissue infection due to a multidrug-resistant organism (MDRO) and recommends standard spectrum antibiotics for low risk patients in the first 3 days of hospitalization; (2) clinician feedback reports, and (3) activities to support CPOE adoption (including education and alignment of CPOE workflows). Other antibiotic stewardship activities to continue in accordance with national standards.
Extended-Spectrum Days of Antibacterial Therapy (ES-DOT) Per Empiric Day Baseline (12 months)	43305 Extended-Spectrum Days-of-Therapy	40156 Extended-Spectrum Days-of-Therapy
Extended-Spectrum Days of Antibacterial Therapy (ES-DOT) Per Empiric Day Intervention (12 months)	43927 Extended-Spectrum Days-of-Therapy	30287 Extended-Spectrum Days-of-Therapy

SECONDARY outcome

Timeframe: First 3 calendar days of hospitalization for each patient during the 12-month baseline and 12-month intervention periods

Population: The total number of participants analyzed reported here is from the baseline and intervention periods

Days-of-Therapy is a standardized national measure for antibacterial use in hospitals that counts each different antibiotic administered on each calendar day as one day of therapy, regardless of doses given. Antipseudomonal days-of-therapy per empiric day is defined as the summed number of different antipseudomonal antibiotics received per patient each calendar day, beginning at admission. If an admission is less than 3 days, only the number of days the patient is admitted will contribute to the numerator and denominator. For example, 2 different antipseudomonal antibiotics administered at least once during each of the first 3 days would yield 6 days of antipseudomonal days-of-therapy.

Outcome measures

Outcome measures
Measure	Arm 1: Routine Stewardship n=60932 Participants Continuation of routine antibiotic stewardship strategies. Arm 1: Routine Care: Routine Antibiotic Stewardship Arm - Continuation of antibiotic stewardship activities in accordance with national standards.	Arm 2: INSPIRE CPOE Bundle n=57630 Participants Use of computerized physician order entry (CPOE) smart prompts, clinician feedback, and activities to support CPOE adoption (including education and alignment of CPOE workflows) to guide empiric choice of antibiotics for skin/soft tissue infection in the first 3 days of hospitalization. Arm 2: INSPIRE Stewardship Bundle for Skin and Soft Tissue Infection: Quality improvement intervention that includes (1) computerized physician order entry (CPOE) decision support alert that provides physicians with patient-specific risk estimates for having a skin/soft tissue infection due to a multidrug-resistant organism (MDRO) and recommends standard spectrum antibiotics for low risk patients in the first 3 days of hospitalization; (2) clinician feedback reports, and (3) activities to support CPOE adoption (including education and alignment of CPOE workflows). Other antibiotic stewardship activities to continue in accordance with national standards.
Antipseudomonal Antibiotic Days Of Therapy (ES-DOT) Per Empiric Day Baseline (12 months)	43305 Antipseudomonal Days-of-Therapy	38059 Antipseudomonal Days-of-Therapy
Antipseudomonal Antibiotic Days Of Therapy (ES-DOT) Per Empiric Day Intervention (12 months)	43927 Antipseudomonal Days-of-Therapy	30287 Antipseudomonal Days-of-Therapy

OTHER_PRE_SPECIFIED outcome

Timeframe: Duration of hospitalization for each patient during 12-month baseline and 12-month intervention periods

Population: The mean number of days to event here is from the the baseline and intervention periods

Days from hospital admission until transfer to ICU, if that occurs. If it doesn't occur, the number of days is censored (capped) at the patient's hospital discharge or at the end of data collection. Almost all patients will be discharged before the end of trial data collection.

Outcome measures

Outcome measures
Measure	Arm 1: Routine Stewardship n=60932 Participants Continuation of routine antibiotic stewardship strategies. Arm 1: Routine Care: Routine Antibiotic Stewardship Arm - Continuation of antibiotic stewardship activities in accordance with national standards.	Arm 2: INSPIRE CPOE Bundle n=57630 Participants Use of computerized physician order entry (CPOE) smart prompts, clinician feedback, and activities to support CPOE adoption (including education and alignment of CPOE workflows) to guide empiric choice of antibiotics for skin/soft tissue infection in the first 3 days of hospitalization. Arm 2: INSPIRE Stewardship Bundle for Skin and Soft Tissue Infection: Quality improvement intervention that includes (1) computerized physician order entry (CPOE) decision support alert that provides physicians with patient-specific risk estimates for having a skin/soft tissue infection due to a multidrug-resistant organism (MDRO) and recommends standard spectrum antibiotics for low risk patients in the first 3 days of hospitalization; (2) clinician feedback reports, and (3) activities to support CPOE adoption (including education and alignment of CPOE workflows). Other antibiotic stewardship activities to continue in accordance with national standards.
Intensive Care Unit (ICU) Transfer [Safety Outcome 1] Baseline (12 months)	5.9 Days to event Standard Deviation 2.8	6.1 Days to event Standard Deviation 2.9
Intensive Care Unit (ICU) Transfer [Safety Outcome 1] Intervention (12 months)	6.3 Days to event Standard Deviation 3.2	6.3 Days to event Standard Deviation 3.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Duration of hospitalization for each patient during 12-month baseline and 12-month intervention periods

Population: The mean number of days to event here is from the baseline and intervention periods

Days from hospital admission until discharge. If the patient remains in the hospital at the end of the trial data collection, the number of days is censored (capped) at that time. Almost all patients will be discharged before the end of trial data collection.

Outcome measures

Outcome measures
Measure	Arm 1: Routine Stewardship n=60932 Participants Continuation of routine antibiotic stewardship strategies. Arm 1: Routine Care: Routine Antibiotic Stewardship Arm - Continuation of antibiotic stewardship activities in accordance with national standards.	Arm 2: INSPIRE CPOE Bundle n=57630 Participants Use of computerized physician order entry (CPOE) smart prompts, clinician feedback, and activities to support CPOE adoption (including education and alignment of CPOE workflows) to guide empiric choice of antibiotics for skin/soft tissue infection in the first 3 days of hospitalization. Arm 2: INSPIRE Stewardship Bundle for Skin and Soft Tissue Infection: Quality improvement intervention that includes (1) computerized physician order entry (CPOE) decision support alert that provides physicians with patient-specific risk estimates for having a skin/soft tissue infection due to a multidrug-resistant organism (MDRO) and recommends standard spectrum antibiotics for low risk patients in the first 3 days of hospitalization; (2) clinician feedback reports, and (3) activities to support CPOE adoption (including education and alignment of CPOE workflows). Other antibiotic stewardship activities to continue in accordance with national standards.
Length-of-stay [Safety Outcome 2] Baseline (12 months)	6.2 Days to event Standard Deviation 3.7	6.1 Days to event Standard Deviation 3.6
Length-of-stay [Safety Outcome 2] Intervention (12 months)	6.5 Days to event Standard Deviation 3.8	6.4 Days to event Standard Deviation 3.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Shruti Gohil, MD, MPH

Division of Infectious Diseases, University of California Irvine School of Medicine

Phone: (714) 456-7890

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm 1: Routine Stewardship n=60932 Participants Continuation of routine antibiotic stewardship strategies. Arm 1: Routine Care: Routine Antibiotic Stewardship Arm - Continuation of antibiotic stewardship activities in accordance with national standards.	Arm 2: INSPIRE CPOE Bundle n=57630 Participants Use of computerized physician order entry (CPOE) smart prompts, clinician feedback, and activities to support CPOE adoption (including education and alignment of CPOE workflows) to guide empiric choice of antibiotics for skin/soft tissue infection in the first 3 days of hospitalization. Arm 2: INSPIRE Stewardship Bundle for Skin and Soft Tissue Infection: Quality improvement intervention that includes (1) computerized physician order entry (CPOE) decision support alert that provides physicians with patient-specific risk estimates for having a skin/soft tissue infection due to a multidrug-resistant organism (MDRO) and recommends standard spectrum antibiotics for low risk patients in the first 3 days of hospitalization; (2) clinician feedback reports, and (3) activities to support CPOE adoption (including education and alignment of CPOE workflows). Other antibiotic stewardship activities to continue in accordance with national standards.	Total n=118562 Participants Total of all reporting groups
Age, Continuous Baseline (12 months)	58 years STANDARD_DEVIATION 18 • n=29595 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	58 years STANDARD_DEVIATION 18 • n=28242 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	58 years STANDARD_DEVIATION 18 • n=57837 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Age, Continuous Intervention (12 months)	59 years STANDARD_DEVIATION 18 • n=31337 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	58 years STANDARD_DEVIATION 17 • n=29388 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	59 years STANDARD_DEVIATION 18 • n=60725 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Sex/Gender, Customized Baseline (12 months) · Female	13087 Participants n=29595 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	12377 Participants n=28242 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	25464 Participants n=57837 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Sex/Gender, Customized Baseline (12 months) · Male	16320 Participants n=29595 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	15719 Participants n=28242 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	32039 Participants n=57837 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Sex/Gender, Customized Baseline (12 months) · Unknown	188 Participants n=29595 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	146 Participants n=28242 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	334 Participants n=57837 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Sex/Gender, Customized Intervention (12 months) · Female	13356 Participants n=31337 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	17015 Participants n=29388 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	30371 Participants n=60725 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Sex/Gender, Customized Intervention (12 months) · Male	17979 Participants n=31337 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	12373 Participants n=29388 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	30352 Participants n=60725 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Sex/Gender, Customized Intervention (12 months) · Unknown	2 Participants n=31337 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	0 Participants n=29388 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	2 Participants n=60725 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Race/Ethnicity, Customized Baseline (12 months) · Black	3052 Participants n=29595 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	3638 Participants n=28242 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	6690 Participants n=57837 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Race/Ethnicity, Customized Baseline (12 months) · White	23153 Participants n=29595 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	20730 Participants n=28242 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	43883 Participants n=57837 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Race/Ethnicity, Customized Baseline (12 months) · Other	1246 Participants n=29595 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	687 Participants n=28242 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	1933 Participants n=57837 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Race/Ethnicity, Customized Baseline (12 months) · Unknown	2144 Participants n=29595 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	3187 Participants n=28242 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	5331 Participants n=57837 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Race/Ethnicity, Customized Intervention (12 months) · Black	3672 Participants n=31337 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	3989 Participants n=29388 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	7661 Participants n=60725 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Race/Ethnicity, Customized Intervention (12 months) · White	23385 Participants n=31337 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	20885 Participants n=29388 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	44270 Participants n=60725 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Race/Ethnicity, Customized Intervention (12 months) · Other	685 Participants n=31337 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	333 Participants n=29388 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	1018 Participants n=60725 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.
Race/Ethnicity, Customized Intervention (12 months) · Unknown	3595 Participants n=31337 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	4181 Participants n=29388 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.	7776 Participants n=60725 Participants • Small differences in the number of patients with various characteristics reflect missing data in the electronic health record.