Trial Outcomes & Findings for Procalcitonin Antibiotic Consensus Trial (ProACT) (NCT NCT02130986)

NCT ID: NCT02130986

Last Updated: 2019-01-15

Results Overview

Total antibiotic exposure, defined as the total number of antibiotic-days by Day 30.

Recruitment status

COMPLETED

Study phase

Target enrollment

1664 participants

Primary outcome timeframe

30 days

Results posted on

2019-01-15

Participant Flow

Subjects were enrolled in the Emergency Department (ED) if they had a primary clinical diagnosis of acute Lower Respiratory Tract Infection \[LRTI\] (\< 28 days duration) and their key clinician was willing to consider Procalcitonin (PCT) result in Antibiotic (ABX) decision making.

Only 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate.

Participant milestones

Participant milestones
Measure	Procalcitonin (PCT) Group Procalcitonin (PCT) Results of procalcitonin level provided to treating clinician (initial in the ED, 6-24 hrs after initial. and Day 3, 5, 7 if in hospital AND on abx or at the treating clinician's discretion) Telephone Visit at Day 15 and Day 30 to collect ABX days, post-d/c resource use and AQ-20 questionnaire Bio-bank samples collected in ED for storage at Coordinating Center	Usual Care (UC) Group Usual Care Telephone Visit at Day 15 and Day 30 to collect ABX days, post-d/c resource use and AQ-20 questionnaire Bio-bank samples collected in ED for storage at Coordinating Center
Overall Study STARTED	830	834
Overall Study COMPLETED	675	670
Overall Study NOT COMPLETED	155	164

Reasons for withdrawal

Reasons for withdrawal
Measure	Procalcitonin (PCT) Group Procalcitonin (PCT) Results of procalcitonin level provided to treating clinician (initial in the ED, 6-24 hrs after initial. and Day 3, 5, 7 if in hospital AND on abx or at the treating clinician's discretion) Telephone Visit at Day 15 and Day 30 to collect ABX days, post-d/c resource use and AQ-20 questionnaire Bio-bank samples collected in ED for storage at Coordinating Center	Usual Care (UC) Group Usual Care Telephone Visit at Day 15 and Day 30 to collect ABX days, post-d/c resource use and AQ-20 questionnaire Bio-bank samples collected in ED for storage at Coordinating Center
Overall Study Withdrawal by Subject	4	4
Overall Study Lost to Follow-up	151	160

Baseline Characteristics

Race and ethnic group were reported by the patients.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Procalcitonin (PCT) Group n=826 Participants Procalcitonin level: A procalcitonin (PCT) will be drawn level within one hour after randomization in the ED, and if hospitalized, 6-24 hours after the initial ED blood draw, and on Days 3, 5, and 7. Days 3, 5, and 7 blood draws for procalcitonin will only occur in hospitalized patients on antibiotics and/or at the treating physician's discretion. Results of procalcitonin (PCT) level to treating clinician: In the ED, we will quickly (\<1 hour goal) provide clinicians the procalcitonin result. Provide PCT guideline to treating clinician: Procalcitonin antibiotic guideline -- PCT level (ug/L)-- Bacterial etiology -- Recommendation \< 0.1-- Very unlikely -- Antibiotics strongly discouraged 0.1 - 0.25 -- Unlikely--Antibiotics discouraged \> 0.25 - 0.5--Likely -- Antibiotics recommended \> 0.5-- Very likely -- Antibiotics strongly recommended Telephone Visit: We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30	Usual Care (UC) Group n=830 Participants Telephone Visit at Day 15 and Day 30 Telephone Visit: We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30	Total n=1656 Participants Total of all reporting groups
Age, Categorical <=18 years	5 Participants n=826 Participants	7 Participants n=830 Participants	12 Participants n=1656 Participants
Age, Categorical Between 18 and 65 years	603 Participants n=826 Participants	596 Participants n=830 Participants	1199 Participants n=1656 Participants
Age, Categorical >=65 years	218 Participants n=826 Participants	227 Participants n=830 Participants	445 Participants n=1656 Participants
Age, Continuous	52.9 years STANDARD_DEVIATION 18.4 • n=826 Participants	53.2 years STANDARD_DEVIATION 18.7 • n=830 Participants	53.1 years STANDARD_DEVIATION 18.5 • n=1656 Participants
Sex: Female, Male Female	469 Participants n=826 Participants	476 Participants n=830 Participants	945 Participants n=1656 Participants
Sex: Female, Male Male	357 Participants n=826 Participants	354 Participants n=830 Participants	711 Participants n=1656 Participants
Race/Ethnicity, Customized White	455 Participants n=826 Participants	470 Participants n=830 Participants	925 Participants n=1656 Participants
Race/Ethnicity, Customized Black	296 Participants n=826 Participants	297 Participants n=830 Participants	593 Participants n=1656 Participants
Race/Ethnicity, Customized Hispanic	108 Participants n=815 Participants • Race and ethnic group were reported by the patients.	104 Participants n=812 Participants • Race and ethnic group were reported by the patients.	212 Participants n=1627 Participants • Race and ethnic group were reported by the patients.
Region of Enrollment United States	826 participants n=826 Participants	830 participants n=830 Participants	1656 participants n=1656 Participants

PRIMARY outcome

Timeframe: 30 days

Population: Mixed modeling was used to impute missing data for the intention-to-treat analysis for the primary outcome since not all patients could be reached for the 30 day interview (which collected 30 day antibiotic use).

Total antibiotic exposure, defined as the total number of antibiotic-days by Day 30.

Outcome measures

Outcome measures
Measure	Procalcitonin (PCT) Group n=826 Participants Procalcitonin (PCT) level; Results of procalcitonin level to treating clinician; Provide procalcitonin guideline to treating clinician; Telephone Visit at Day 15 and Day 30 Procalcitonin level: A procalcitonin (PCT) will be drawn level within one hour after randomization in the ED, and if hospitalized, 6-24 hours after the initial ED blood draw, and on Days 3, 5, and 7. Days 3, 5, and 7 blood draws for procalcitonin will only occur in hospitalized patients on antibiotics and/or at the treating physician's discretion. Results of procalcitonin (PCT) level to treating clinician: In the ED, we will quickly (\<1 hour goal) provide clinicians the procalcitonin result. Provide procalcitonin guideline to treating clinician.	Usual Care Group n=830 Participants Telephone Visit at Day 15 and Day 30 Telephone Visit: We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30
Total Antibiotic Exposure Days	4.2 days Standard Deviation 5.8	4.3 days Standard Deviation 5.6

PRIMARY outcome

Timeframe: 30 days

Primary Safety Outcome - Combined endpoint of adverse outcomes (death, endotracheal intubation, vasopressors, renal failure, lung abscess/empyema, pneumonia in non-CAP patient, and hospital readmissions) that could be attributable to withholding antibiotics in lower respiratory tract infection (LRTI). Number is based on the number of participants that experienced any adverse outcome.

Outcome measures

Outcome measures
Measure	Procalcitonin (PCT) Group n=826 Participants Procalcitonin (PCT) level; Results of procalcitonin level to treating clinician; Provide procalcitonin guideline to treating clinician; Telephone Visit at Day 15 and Day 30 Procalcitonin level: A procalcitonin (PCT) will be drawn level within one hour after randomization in the ED, and if hospitalized, 6-24 hours after the initial ED blood draw, and on Days 3, 5, and 7. Days 3, 5, and 7 blood draws for procalcitonin will only occur in hospitalized patients on antibiotics and/or at the treating physician's discretion. Results of procalcitonin (PCT) level to treating clinician: In the ED, we will quickly (\<1 hour goal) provide clinicians the procalcitonin result. Provide procalcitonin guideline to treating clinician.	Usual Care Group n=830 Participants Telephone Visit at Day 15 and Day 30 Telephone Visit: We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30
Number of Participants With Any Adverse Outcome	96 Participants	109 Participants

SECONDARY outcome

Timeframe: While in the ED or before ED discharge (majority patients < 1 day)

Antibiotic prescription in the ED includes post-randomization receipt of antibiotics in ED and provision of an antibiotic prescription for patients at the time of discharge from the ED.

Outcome measures

Outcome measures
Measure	Procalcitonin (PCT) Group n=826 Participants Procalcitonin (PCT) level; Results of procalcitonin level to treating clinician; Provide procalcitonin guideline to treating clinician; Telephone Visit at Day 15 and Day 30 Procalcitonin level: A procalcitonin (PCT) will be drawn level within one hour after randomization in the ED, and if hospitalized, 6-24 hours after the initial ED blood draw, and on Days 3, 5, and 7. Days 3, 5, and 7 blood draws for procalcitonin will only occur in hospitalized patients on antibiotics and/or at the treating physician's discretion. Results of procalcitonin (PCT) level to treating clinician: In the ED, we will quickly (\<1 hour goal) provide clinicians the procalcitonin result. Provide procalcitonin guideline to treating clinician.	Usual Care Group n=830 Participants Telephone Visit at Day 15 and Day 30 Telephone Visit: We will collect the number of antibiotic days during telephone visits occurring on or around Day 15 and Day 30
Antibiotic Prescription in Emergency Department(ED)	282 Participants	321 Participants

Adverse Events

Procalcitonin (PCT) Group

Serious events: 14 serious events

Other events: 20 other events

Deaths: 16 deaths

Usual Care Group

Serious events: 9 serious events

Other events: 14 other events

Deaths: 10 deaths

Serious adverse events

Other adverse events

Additional Information

David T Huang, MD, MPH, Associate Professor

University of Pittsburgh

Phone: 412-647-6818

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Procalcitonin (PCT) Group n=826 participants at risk Procalcitonin (PCT) Results of procalcitonin level provided to treating clinician (initial in the ED, 6-24 hrs after initial. and Day 3, 5, 7 if in hospital AND on abx or at the treating clinician's discretion) Telephone Visit at Day 15 and Day 30 to collect ABX days, post-d/c resource use and AQ-20 questionnaire Bio-bank samples collected in ED for storage at Coordinating Center	Usual Care Group n=830 participants at risk Usual Care Telephone Visit at Day 15 and Day 30 to collect ABX days, post-d/c resource use and AQ-20 questionnaire Bio-bank samples collected in ED for storage at Coordinating Center
Respiratory, thoracic and mediastinal disorders Dyspnea	0.24% 2/826 • Number of events 2 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.12% 1/830 • Number of events 1 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
General disorders Death NOS	0.36% 3/826 • Number of events 3 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.00% 0/830 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Gastrointestinal disorders Gastritis	0.00% 0/826 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.12% 1/830 • Number of events 1 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Infections and infestations Sepsis	0.00% 0/826 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.12% 1/830 • Number of events 1 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Nervous system disorders Stroke	0.00% 0/826 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.12% 1/830 • Number of events 1 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Cardiac disorders Cardiac arrest	0.00% 0/826 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.24% 2/830 • Number of events 2 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Blood and lymphatic system disorders Anemia	0.12% 1/826 • Number of events 1 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.00% 0/830 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Immune system disorders Immune system disorders	0.00% 0/826 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.00% 0/830 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	0.00% 0/826 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.00% 0/830 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Renal and urinary disorders Acute kidney injury	0.12% 1/826 • Number of events 1 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.00% 0/830 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Vascular disorders Hypotension	0.00% 0/826 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.12% 1/830 • Number of events 1 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.24% 2/826 • Number of events 2 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.00% 0/830 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	0.00% 0/826 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.12% 1/830 • Number of events 1 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.24% 2/826 • Number of events 2 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.00% 0/830 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	0.12% 1/826 • Number of events 1 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.00% 0/830 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Cardiac disorders Heart failure	0.00% 0/826 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.12% 1/830 • Number of events 1 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.12% 1/826 • Number of events 1 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.00% 0/830 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.
General disorders Pain	0.12% 1/826 • Number of events 1 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.	0.00% 0/830 • By day 30. All events were reviewed and assessed by the Principal Investigator at the participating site. 8 patients (4 in each arm) were entirely excluded because they withdrew all consent to participate. Most specific terms are reported in the Adverse Event Section.