Trial Outcomes & Findings for Rapid Identification and Phenotypic Susceptibility Testing for Gram-Negative Bacteremia (NCT NCT03218397)

NCT ID: NCT03218397

Last Updated: 2019-11-26

Results Overview

Mean hours until first modification of antibiotic therapy within 72 hours post randomization

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 500 participants
• Primary outcome timeframe: 72 hours after randomization
• Results posted on: 2019-11-26

Participant Flow

Participant milestones

Measure	Standard Blood Culture and AST Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Overall Study STARTED	249	251
Overall Study COMPLETED	226	222
Overall Study NOT COMPLETED	23	29

Reasons for withdrawal

Measure	Standard Blood Culture and AST Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Overall Study Prior positive blood culture	8	13
Overall Study Comfort care	8	5
Overall Study Comfort care and positive blood culture	1	0
Overall Study Comfort care and mixed culture	0	1
Overall Study Mixed culture	2	2
Overall Study Inaccessible hospital records	2	5
Overall Study No gram-negative bacilli (GNB)	0	2
Overall Study Randomized during laboratory off hours	2	1

Baseline Characteristics

Rapid Identification and Phenotypic Susceptibility Testing for Gram-Negative Bacteremia

Baseline characteristics by cohort

Measure	Standard Blood Culture and AST n=226 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=222 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.	Total n=448 Participants Total of all reporting groups
Age, Continuous	65.8 years STANDARD_DEVIATION 18.3 • n=5 Participants	62.2 years STANDARD_DEVIATION 20.3 • n=7 Participants	64.0 years STANDARD_DEVIATION 19.4 • n=5 Participants
Sex/Gender, Customized Male	130 Participants n=5 Participants	122 Participants n=7 Participants	252 Participants n=5 Participants
Sex/Gender, Customized Female	95 Participants n=5 Participants	100 Participants n=7 Participants	195 Participants n=5 Participants
Sex/Gender, Customized Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	16 Participants n=7 Participants	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	202 Participants n=5 Participants	191 Participants n=7 Participants	393 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	15 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) White	183 Participants n=5 Participants	176 Participants n=7 Participants	359 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	21 Participants n=5 Participants	26 Participants n=7 Participants	47 Participants n=5 Participants
Region of Enrollment United States	226 Participants n=5 Participants	222 Participants n=7 Participants	448 Participants n=5 Participants

PRIMARY outcome

Timeframe: 72 hours after randomization

Population: Subjects who completed the study.

Mean hours until first modification of antibiotic therapy within 72 hours post randomization

Outcome measures

Measure	Standard Blood Culture and AST n=226 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=222 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Hours to First Antibiotic Modification	24.7 hours Standard Deviation 24.6	19.0 hours Standard Deviation 22.9

SECONDARY outcome

Timeframe: Within 30 days of randomization

Population: Subjects who completed the study.

Subjects who experienced mortality within 30 days of randomization

Outcome measures

Measure	Standard Blood Culture and AST n=226 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=222 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Subjects Who Experienced Mortality Within 30 Days of Randomization Dead within 30 days	18 Participants	25 Participants
Subjects Who Experienced Mortality Within 30 Days of Randomization Not dead within 30 days	206 Participants	197 Participants
Subjects Who Experienced Mortality Within 30 Days of Randomization Unknown	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Within 30 days of randomization

Population: Subjects who were alive at 30 days.

Length of stay in the hospital after randomization, up to 30 days, for patients alive at 30 days. Length of stay will be date of discharge minus date of randomization.

Outcome measures

Measure	Standard Blood Culture and AST n=208 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=197 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Length of Stay in the Hospital	8.2 days Standard Deviation 8.7	9.8 days Standard Deviation 9.8

SECONDARY outcome

Timeframe: Within 72 hours of randomization

Population: Subjects who completed the study.

ICU status through 72 hours post-randomization

Outcome measures

Measure	Standard Blood Culture and AST n=226 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=222 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
ICU Status Through 72 Hours Post-randomization In ICU < 72 hours after randomization	33 Participants	55 Participants
ICU Status Through 72 Hours Post-randomization In ICU for >= 72 hours after randomization	34 Participants	37 Participants
ICU Status Through 72 Hours Post-randomization Not in ICU	159 Participants	130 Participants

SECONDARY outcome

Timeframe: Within 72 hours of randomization

Population: Subjects who completed the study.

Mean hours to first antibiotic escalation within 72 hours from randomization, where escalation is defined as changing to a broader spectrum antibiotic, addition of one or more antibiotics, or conversion of oral to intravenous route.

Outcome measures

Measure	Standard Blood Culture and AST n=226 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=222 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Time to First Antibiotic Escalation	52.7 hours Standard Deviation 28.8	45.2 hours Standard Deviation 31.4

SECONDARY outcome

Timeframe: Within 72 hours of randomization

Population: Subjects who completed the study.

Mean hours to first gram-negative antibiotic escalation within 72 hours from randomization, where escalation is defined as changing to a broader spectrum antibiotic, addition of one or more antibiotics, or conversion of oral to intravenous route.

Outcome measures

Measure	Standard Blood Culture and AST n=226 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=222 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Time to First Gram-negative Antibiotic Escalation	53.9 hours Standard Deviation 28.4	47.5 hours Standard Deviation 31.2

SECONDARY outcome

Timeframe: Within 72 hours of randomization

Population: Subjects who completed the study.

Mean hours to first gram-positive antibiotic escalation within 72 hours from randomization, where escalation is defined as changing to a broader spectrum antibiotic, addition of one or more antibiotics, or conversion of oral to intravenous route.

Outcome measures

Measure	Standard Blood Culture and AST n=226 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=222 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Time to First Gram-positive Antibiotic Escalation	70.5 hours Standard Deviation 9.5	69.7 hours Standard Deviation 11.3

SECONDARY outcome

Timeframe: Within 72 hours of randomization

Population: Subjects who completed the study.

Mean hours to first antibiotic de-escalation within 72 hours from randomization, where de-escalation is defined as changing to a narrower spectrum antibiotic, cessation of one or more antibiotics, or changing from an intravenous to oral route of appropriate drug.

Outcome measures

Measure	Standard Blood Culture and AST n=226 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=222 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Time to First Antibiotic De-escalation	44.2 hours Standard Deviation 26.2	39.6 hours Standard Deviation 28.0

SECONDARY outcome

Timeframe: Within 72 hours of randomization

Population: Subjects who completed the study.

Mean hours to first gram-negative antibiotic de-escalation within 72 hours from randomization, where de-escalation is defined as changing to a narrower spectrum antibiotic, cessation of one or more antibiotics, or changing from an intravenous to oral route of appropriate drug.

Outcome measures

Measure	Standard Blood Culture and AST n=226 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=222 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Time to First Gram-negative Antibiotic De-escalation	55.8 hours Standard Deviation 23.5	49.3 hours Standard Deviation 27.8

SECONDARY outcome

Timeframe: Within 72 hours of randomization

Population: Subjects who completed the study.

Mean hours to first gram-positive antibiotic de-escalation within 72 hours from randomization, where de-escalation is defined as changing to a narrower spectrum antibiotic, cessation of one or more antibiotics, or changing from an intravenous to oral route of appropriate drug.

Outcome measures

Measure	Standard Blood Culture and AST n=226 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=222 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Time to First Gram-positive Antibiotic De-escalation	60.4 hours Standard Deviation 22.6	62.2 hours Standard Deviation 21.3

SECONDARY outcome

Timeframe: Within 30 days of randomization

Population: Subjects who completed the study.

Acquisition of hospital-onset Clostridium difficile within 30 days, as defined by the National Healthcare Safety Network (NHSN), normalized to 10,000 patient-days.

Outcome measures

Measure	Standard Blood Culture and AST n=226 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=222 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Number of Hospital-onset Clostridium Difficile Infections	26.8 Infections per 10,000 patient-days Interval 11.2 to 64.4	27.5 Infections per 10,000 patient-days Interval 12.4 to 61.3

SECONDARY outcome

Timeframe: Within 30 days of randomization

Population: Subjects who completed the study.

Acquisition of new hospital-acquired infections (HAIs) and/or multidrug resistant organisms (MDROs) within 30 days during index hospitalization identified on routine clinical or surveillance samples.

Cultures that will be tracked include the following, from any specimen source, unless otherwise indicated:

• Methicillin-resistant Staphylococcus aureus
• Vancomycin-resistant Enterococcus
• 3rd generation cephalosporin non-susceptible Enterobacteriaceae
• Carbapenem-resistant Enterobacteriaceae, as defined by the Centers for Disease Control and Prevention (CDC): resistant to imipenem, meropenem, doripenem, or ertapenem OR documentation that the isolate possesses a carbapenemase
• Multidrug-resistant Pseudomonas aeruginosa (resistant to aminoglycosides, cephalosporins, fluoroquinolones, and carbapenems)
• Carbapenem-resistant Acinetobacter
• Candida species (isolated from blood cultures only)

Outcome measures

Measure	Standard Blood Culture and AST n=226 Participants Standard blood culture and antimicrobial susceptibility testing (AST), and antimicrobial stewardship.	Rapid Organism Identification and AST n=222 Participants Rapid organism identification and AST using the Accelerate PhenoTest™ BC Kit, performed on the Accelerate Pheno™ System (AXDX), and antimicrobial stewardship. The blood sample will also undergo standard culture and AST in addition to the rapid testing.
Number of New Hospital-acquired Infections (HAIs) and/or Multidrug Resistant Organisms (MDROs), Normalized to 10,000 Patient-days.	123.3 Infections per 10,000 patient-days Interval 82.0 to 185.6	105.5 Infections per 10,000 patient-days Interval 70.1 to 158.8

Adverse Events

Standard Blood Culture and AST

Serious events: 0 serious events

Other events: 0 other events

Deaths: 18 deaths

Rapid Organism Identification and AST

Serious events: 0 serious events

Other events: 0 other events

Deaths: 25 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Vance Fowler, MD, MHS

Duke University

Phone: 919-613-5678

Email: vance.fowler@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place