TARPP: Trial of Antimicrobial Restraint in Presumed Pneumonia

Sponsor

University of Kansas Medical Center (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04438187

Collaborator

Western Michigan University (Other)

200

Enrollment

Location

Arms

13.9

Anticipated Duration (Months)

14.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this cluster-randomized crossover study is to determine the effect of delaying antimicrobial initiation until objective microbiologic data is obtained in patients with presumed ICU-acquired pneumonia without septic shock.

Condition or Disease	Intervention/Treatment	Phase
Healthcare-Associated Pneumonia Sepsis	Other: antimicrobial initiation	N/A

Detailed Description

This study will involve 8 centers is to determine the effect of delaying antimicrobial initiation until objective microbiologic data is obtained in patients with presumed ICU-acquired pneumonia without septic shock. The study team will compare two sequential 4-month periods in each unit, one 'aggressive' antimicrobial initiation period and one 'conservative' antimicrobial initiation period.

This study will serve the following specific aims:

Specific Aim 1: To determine feasibility of a larger multicenter study of the same design as well as assess protocol adherence across multiple centers.

Specific Aim 2: Prospectively determine the all-cause, in-hospital mortality for all patients with suspected pneumonia who were treated under either an aggressive or conservative antimicrobial initiation protocol.

Specific Aim 3: Prospectively determine antimicrobial initiation rates, total days of antimicrobial administration, hospital and ICU length of stay, and ventilator-free alive days for patients treated under each protocol.

Specific Aim 4: To survey physicians that participated in the study to assess their feelings about the study including level of comfort starting antimicrobials aggressively, level of comfort withholding antimicrobials until definitive evidence of infection, perceived protocol adherence, perceived importance of the study, and willingness to participate in other studies of its kind (to be performed after closure of the clinical portion of the study).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

This will be a pragmatic, before-and-after, cluster-randomized, protocol crossover study.This will be a pragmatic, before-and-after, cluster-randomized, protocol crossover study.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Trial of Antimicrobial Restraint in Presumed Pneumonia

Actual Study Start Date :

Feb 1, 2021

Anticipated Primary Completion Date :

Oct 31, 2021

Anticipated Study Completion Date :

Mar 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Other: Aggressive Arm If an intubated patient is suspected of having an ICU-acquired HAP/VAP during the aggressive period, antimicrobials should be initiated immediately after quantitative or semi-quantitative endobronchial cultures are sent regardless of clinical status. This will include patients who, as determined by the attending intensivist, are in sepsis or septic shock. If, after 72 hours, cultures and other clinical data do not point to a pneumonia, the antimicrobials should be stopped in the absence of another source of infection.	Other: antimicrobial initiation antimicrobial initiation based on protocol assignment.
Other: Conservative Arm If a patient is suspected of having an ICU-acquired HAP/VAP during the conservative period, quantitative or semi-quantitative endobronchial cultures should be sent. If the patient is in septic shock persistent hypotension requiring vasoactive medications to maintain mean arterial pressure (MAP) ≥65 mm HG or persistent lactic acidosis (>2 mmol/L) despite adequate resuscitation) antimicrobials will be initiated immediately. If the patient has new onset organ dysfunction that is presumed to be due to infection (sepsis) then antimicrobials will be initiated at the discretion of the attending intensivist. In the absence of septic shock or sepsis (intensivist discretion), antimicrobials will not be initiated unless objective evidence of pneumonia is present or another documented source of infection is identified mandating treatment with antimicrobials.	Other: antimicrobial initiation antimicrobial initiation based on protocol assignment.

Arm

Intervention/Treatment

Other: Aggressive Arm

If an intubated patient is suspected of having an ICU-acquired HAP/VAP during the aggressive period, antimicrobials should be initiated immediately after quantitative or semi-quantitative endobronchial cultures are sent regardless of clinical status. This will include patients who, as determined by the attending intensivist, are in sepsis or septic shock. If, after 72 hours, cultures and other clinical data do not point to a pneumonia, the antimicrobials should be stopped in the absence of another source of infection.

Other: antimicrobial initiation

antimicrobial initiation based on protocol assignment.

Other: Conservative Arm

If a patient is suspected of having an ICU-acquired HAP/VAP during the conservative period, quantitative or semi-quantitative endobronchial cultures should be sent. If the patient is in septic shock persistent hypotension requiring vasoactive medications to maintain mean arterial pressure (MAP) ≥65 mm HG or persistent lactic acidosis (>2 mmol/L) despite adequate resuscitation) antimicrobials will be initiated immediately. If the patient has new onset organ dysfunction that is presumed to be due to infection (sepsis) then antimicrobials will be initiated at the discretion of the attending intensivist. In the absence of septic shock or sepsis (intensivist discretion), antimicrobials will not be initiated unless objective evidence of pneumonia is present or another documented source of infection is identified mandating treatment with antimicrobials.

Other: antimicrobial initiation

antimicrobial initiation based on protocol assignment.

Outcome Measures

Primary Outcome Measures

protocol adherence [by time of culture finalization or 1 week]
as a pilot study the primary outcome will be protocol adherence as defined by using the criteria below: Aggressive Protocol: Failure to send appropriate culture before initiation of antimicrobials in the absence of septic shock Failure to stop antimicrobials in the absence of pneumonia or other documented infection after 72 hours. Conservative Protocol: Failure to send appropriate culture Initiation of antimicrobials (in the absence of septic shock, new onset or worsening organ dysfunction, or other indicated source of infection) without any objective evidence of pneumonia. Failure to initiate antimicrobials in the setting of objective evidence of pneumonia. Failure to stop antimicrobials in the absence of other documented infection if final cultures return as negative.

Secondary Outcome Measures

In-hospital mortality [until hospital discharge or 1 year]
All-cause, by treatment protocol assignment (intent-to-treat), ICU mortality, pneumonia-related
Days of antimicrobials administered [until hospital discharge or 1 year]
includes empiric, therapeutic, prophylactic, and perioperative antimicrobials
Ventilator-free alive days [until hospital discharge or 1 year]
ICU length of stay [Until discharge from ICU or 1 year]
Hospital length of stay [until hospital discharge or 1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Intubated patients admitted to a surgical or trauma intensive care unit that have had an appropriate quantitative or semi-quantitative endobronchial sputum culture sent ≥48 hours into their ICU admission
Primary pathology managed by surgical specialty
Age ≥18 years.

Exclusion Criteria:

Non-intubated patients.
Intubated patients with concern for active infection that is not suspected to be pneumonia (i.e. intra-abdominal infection, skin and soft tissue infection, urinary tract infection, etc.)
Primary disease not surgical or traumatic in nature
Primary diagnosis of burns
Incarcerated status
Pregnant status or delivery during this hospitalization.
On active immunosuppressive medications (or taking as a home medication prior to arrival)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	KU Medical Center	Kansas City	Kansas	United States	66160

Sponsors and Collaborators

University of Kansas Medical Center
Western Michigan University

Investigators

Principal Investigator: Christopher Guidry, KU Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

University of Kansas Medical Center

ClinicalTrials.gov Identifier:

NCT04438187

Other Study ID Numbers:

145059

First Posted:

Jun 18, 2020

Last Update Posted:

May 14, 2021

Last Verified:

May 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Pneumonia

Healthcare-Associated Pneumonia

Anti-Infective Agents

Anti-Bacterial Agents

Study Results

No Results Posted as of May 14, 2021