Trial of Antimicrobial Restraint in Presumed Pneumonia

Sepsis Clinical Trial

— TARPP  

Official title:

Trial of Antimicrobial Restraint in Presumed Pneumonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04438187
• Other study ID #: 145059
• Status: Completed
• Phase: N/A
• Start date: February 1, 2021
• Est. completion date: June 30, 2022

Study information

• Verified date: November 2022
• Source: University of Kansas Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 186
• Est. completion date: June 30, 2022
• Est. primary completion date: January 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthcare-Associated Pneumonia
• Pneumonia
• Sepsis

Intervention

Other:
• antimicrobial initiation
antimicrobial initiation based on protocol assignment.

Locations

Country	Name	City	State
United States	KU Medical Center	Kansas City	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
University of Kansas Medical Center	Western Michigan University

Country where clinical trial is conducted

United States, 

References & Publications (29)

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de Groot B, Ansems A, Gerling DH, Rijpsma D, van Amstel P, Linzel D, Kostense PJ, Jonker M, de Jonge E. The association between time to antibiotics and relevant clinical outcomes in emergency department patients with various stages of sepsis: a prospective multi-center study. Crit Care. 2015 Apr 29;19:194. doi: 10.1186/s13054-015-0936-3. — View Citation

Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM; Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004 Mar;32(3):858-73. Review. Erratum in: Crit Care Med. 2004 Jun;32(6):1448. Dosage error in article text. Crit Care Med. 2004 Oct;32(10):2169-70. — View Citation

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Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, Artigas A, Schorr C, Levy MM. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014 Aug;42(8):1749-55. doi: 10.1097/CCM.0000000000000330. — View Citation

Gaieski DF, Mikkelsen ME, Band RA, Pines JM, Massone R, Furia FF, Shofer FS, Goyal M. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010 Apr;38(4):1045-53. doi: 10.1097/CCM.0b013e3181cc4824. — View Citation

Hranjec T, Rosenberger LH, Swenson B, Metzger R, Flohr TR, Politano AD, Riccio LM, Popovsky KA, Sawyer RG. Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study. Lancet Infect Dis. 2012 Oct;12(10):774-80. doi: 10.1016/S1473-3099(12)70151-2. Epub 2012 Aug 28. — View Citation

Kaasch AJ, Rieg S, Kuetscher J, Brodt HR, Widmann T, Herrmann M, Meyer C, Welte T, Kern P, Haars U, Reuter S, Hübner I, Strauss R, Sinha B, Brunkhorst FM, Hellmich M, Fätkenheuer G, Kern WV, Seifert H; preSABATO study group. Delay in the administration of appropriate antimicrobial therapy in Staphylococcus aureus bloodstream infection: a prospective multicenter hospital-based cohort study. Infection. 2013 Oct;41(5):979-85. doi: 10.1007/s15010-013-0428-9. Epub 2013 Mar 29. — View Citation

Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O'Grady NP, Bartlett JG, Carratalà J, El Solh AA, Ewig S, Fey PD, File TM Jr, Restrepo MI, Roberts JA, Waterer GW, Cruse P, Knight SL, Brozek JL. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63(5):e61-e111. doi: 10.1093/cid/ciw353. Epub 2016 Jul 14. Erratum in: Clin Infect Dis. 2017 May 1;64(9):1298. Erratum in: Clin Infect Dis. 2017 Oct 15;65(8):1435. Clin Infect Dis. 2017 Nov 29;65(12):2161. — View Citation

Klompas M, Calandra T, Singer M. Antibiotics for Sepsis-Finding the Equilibrium. JAMA. 2018 Oct 9;320(14):1433-1434. doi: 10.1001/jama.2018.12179. — View Citation

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Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96. — View Citation

Leonard KL, Borst GM, Davies SW, Coogan M, Waibel BH, Poulin NR, Bard MR, Goettler CE, Rinehart SM, Toschlog EA. Ventilator-Associated Pneumonia in Trauma Patients: Different Criteria, Different Rates. Surg Infect (Larchmt). 2016 Jun;17(3):363-8. doi: 10.1089/sur.2014.076. Epub 2016 Mar 3. — View Citation

Loftus TJ, Brakenridge SC, Moore FA, Lemon SJ, Nguyen LL, Voils SA, Jordan JR, Croft CA, Smith RS, Efron PA, Mohr AM. Intubated Trauma Patients Receiving Prolonged Antibiotics for Pneumonia despite Negative Cultures: Predictors and Outcomes. Surg Infect (Larchmt). 2016 Dec;17(6):766-772. Epub 2016 Sep 16. — View Citation

Mi MY, Klompas M, Evans L. Early Administration of Antibiotics for Suspected Sepsis. N Engl J Med. 2019 Feb 7;380(6):593-596. doi: 10.1056/NEJMclde1809210. — View Citation

Pieracci FM, Rodil M, Haenel J, Stovall RT, Johnson JL, Burlew CC, Jurkovich GJ, Moore EE. Screening for Ventilator-Associated Pneumonia in the Surgical Intensive Care Unit: A Single-Institution Analysis of 1,013 Lower Respiratory Tract Cultures. Surg Infect (Larchmt). 2015 Aug;16(4):368-74. doi: 10.1089/sur.2014.086. Epub 2015 May 28. — View Citation

Piriyapatsom A, Lin H, Pirrone M, De Pascale G, Corona De Lapuerta J, Bittner EA, Schmidt UH, De Moya M, Berra L. Evaluation of the Infection-Related Ventilator-Associated Events Algorithm for Ventilator-Associated Pneumonia Surveillance in a Trauma Population. Respir Care. 2016 Mar;61(3):269-76. doi: 10.4187/respcare.04280. Epub 2015 Nov 10. — View Citation

Prescott HC, Iwashyna TJ. Improving Sepsis Treatment by Embracing Diagnostic Uncertainty. Ann Am Thorac Soc. 2019 Apr;16(4):426-429. doi: 10.1513/AnnalsATS.201809-646PS. — View Citation

Quick JA, Breite MD, Barnes SL. Inadequacy of Algorithmic Ventilator-Associated Pneumonia Diagnosis in Acute Care Surgery. Am Surg. 2018 Feb 1;84(2):300-304. — View Citation

Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med. 2017 Mar;45(3):486-552. doi: 10.1097/CCM.0000000000002255. — View Citation

Torres A, Niederman MS, Chastre J, Ewig S, Fernandez-Vandellos P, Hanberger H, Kollef M, Li Bassi G, Luna CM, Martin-Loeches I, Paiva JA, Read RC, Rigau D, Timsit JF, Welte T, Wunderink R. International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT). Eur Respir J. 2017 Sep 10;50(3). pii: 1700582. doi: 10.1183/13993003.00582-2017. Print 2017 Sep. — View Citation

* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	protocol adherence	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.	by time of culture finalization or 1 week
Secondary	In-hospital mortality	All-cause, by treatment protocol assignment (intent-to-treat), ICU mortality, pneumonia-related	until hospital discharge or 1 year
Secondary	Days of antimicrobials administered	includes empiric, therapeutic, prophylactic, and perioperative antimicrobials	until hospital discharge or 1 year
Secondary	Ventilator-free alive days		until hospital discharge or 1 year
Secondary	ICU length of stay		Until discharge from ICU or 1 year
Secondary	Hospital length of stay		until hospital discharge or 1 year