Efficacy and Safety of Antimicrobial Stewardship Intervention in Hospitalized COVID-19 Patients (COVASP)

Covid19 Clinical Trial

— COVASP  

Official title:

Efficacy and Safety of Antimicrobial Stewardship Intervention in Hospitalized COVID-19 Patients: A Pragmatic Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04896866
• Other study ID #: Pro00105598
• Status: Completed
• Phase: N/A
• Start date: March 1, 2021
• Est. completion date: November 30, 2021

Study information

• Verified date: April 2023
• Source: University of Alberta
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

COVID-19 is respiratory disease caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2), a novel coronavirus which has spread rapidly across the world with over 149.9 million laboratory confirmed cases and over 3.1 million reported deaths since December 2019. Approximately 4-8% of hospitalized patients with COVID-19 have co-infection with bacterial pathogens however there is widespread and often broad-spectrum antibiotic use in these patients. This is a prospective, multi-center, non-inferiority pragmatic clinical trial of antimicrobial stewardship prospective audit and feedback versus no antimicrobial stewardship intervention on physicians attending to patients with proven SARS-CoV-2 infection confirmed by nucleic acid testing in the preceding 2 weeks of hospitalization for acute COVID-19 pneumonia. Prospective audit and feedback is the real time review of antibacterial prescriptions and immediate feedback to prescribers to optimize antimicrobial prescriptions. Hospital beds will be stratified by COVID unit and critical care unit beds, and will be computer randomized in a 1:1 fashion into 2 arms (antimicrobial stewardship intervention versus no antimicrobial stewardship intervention) prior to study commencement at the participating site. Patients hospitalized to study-eligible beds will be followed for primary and secondary outcomes. The objective of this study is to determine the effect of an antimicrobial stewardship intervention (prospective audit and feedback) on clinical outcomes in patients hospitalized with acute COVID-19.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 833
• Est. completion date: November 30, 2021
• Est. primary completion date: October 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18 years at the time of hospital admission.
• Confirmed SARS-CoV-2 infection by nucleic acid testing in the preceding 14 days of hospital admission.
• Admitted from the community (including continuing care facilities).
• Admitted to a hospital bed designated in the study.
• SpO2 =94% requiring supplemental oxygen or chest imaging findings compatible with COVID-19 pneumonia.

Exclusion Criteria:

• The patient is enrolled in another clinical trial that involves antibacterial therapy.
• The patient's goals of care is anticipated to be designated "total compassionate care" or palliative care within 48 hours of admission.
• The patient's progression to death is anticipated to be imminent and inevitable within 48 hours of admission.
• The patient was attended by any member of the research team within 30 days of enrollment.
• The patient is transferred from another acute care center.

Related Conditions & MeSH terms

• Acute Lung Injury
• Communicable Diseases
• COVID-19
• COVID-19 Pneumonia
• Covid19
• Infections
• Respiration Disorders
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Respiratory Tract Diseases
• Respiratory Tract Infections
• SARS-CoV-2 Acute Respiratory Disease
• SARS-CoV2 Infection

Intervention

Behavioral:
• Antimicrobial stewardship prospective audit and feedback
Audits are performed on weekdays, less statutory holidays, by members of the antimicrobial stewardship team consisting of infectious disease or antimicrobial stewardship physicians or pharmacists. Verbal and written feedback will be provided in real-time. Initial prospective audit and feedback (PAF) will occur on the day of enrolment. Follow-up PAF will occur weekly (+/-3 days to account for weekends or statuary holidays) and ad-hoc if a new antibacterial is prescribed, until the primary end-point. Appropriateness will be assessed based on local clinical practice guidelines. Only antibacterials will be audited. Prescriptions will be excluded from PAF if they are single doses or discontinued prior to PAF. Prescriptions will be also be excluded from PAF and the final analysis if being used for surgical or medical prophylaxis.

Locations

Country	Name	City	State
Canada	Grey Nuns Community Hospital	Edmonton	Alberta
Canada	Misericordia Community Hospital	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Alberta

Country where clinical trial is conducted

Canada, 

References & Publications (19)

Barrasa H, Rello J, Tejada S, Martin A, Balziskueta G, Vinuesa C, Fernandez-Miret B, Villagra A, Vallejo A, San Sebastian A, Cabanes S, Iribarren S, Fonseca F, Maynar J; Alava COVID-19 Study Investigators. SARS-CoV-2 in Spanish Intensive Care Units: Early experience with 15-day survival in Vitoria. Anaesth Crit Care Pain Med. 2020 Oct;39(5):553-561. doi: 10.1016/j.accpm.2020.04.001. Epub 2020 Apr 9. — View Citation

Cao J, Hu X, Cheng W, Yu L, Tu WJ, Liu Q. Clinical features and short-term outcomes of 18 patients with corona virus disease 2019 in intensive care unit. Intensive Care Med. 2020 May;46(5):851-853. doi: 10.1007/s00134-020-05987-7. Epub 2020 Mar 2. No abstract available. Erratum In: Intensive Care Med. 2020 Apr 14;: — View Citation

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30. — View Citation

Clancy CJ, Nguyen MH. Coronavirus Disease 2019, Superinfections, and Antimicrobial Development: What Can We Expect? Clin Infect Dis. 2020 Dec 17;71(10):2736-2743. doi: 10.1093/cid/ciaa524. — View Citation

Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020 May;20(5):533-534. doi: 10.1016/S1473-3099(20)30120-1. Epub 2020 Feb 19. No abstract available. Erratum In: Lancet Infect Dis. 2020 Sep;20(9):e215. — View Citation

Du Y, Tu L, Zhu P, Mu M, Wang R, Yang P, Wang X, Hu C, Ping R, Hu P, Li T, Cao F, Chang C, Hu Q, Jin Y, Xu G. Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study. Am J Respir Crit Care Med. 2020 Jun 1;201(11):1372-1379. doi: 10.1164/rccm.202003-0543OC. — View Citation

Feng Y, Ling Y, Bai T, Xie Y, Huang J, Li J, Xiong W, Yang D, Chen R, Lu F, Lu Y, Liu X, Chen Y, Li X, Li Y, Summah HD, Lin H, Yan J, Zhou M, Lu H, Qu J. COVID-19 with Different Severities: A Multicenter Study of Clinical Features. Am J Respir Crit Care Med. 2020 Jun 1;201(11):1380-1388. doi: 10.1164/rccm.202002-0445OC. — View Citation

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;: — View Citation

Langford BJ, So M, Raybardhan S, Leung V, Westwood D, MacFadden DR, Soucy JR, Daneman N. Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis. Clin Microbiol Infect. 2020 Dec;26(12):1622-1629. doi: 10.1016/j.cmi.2020.07.016. Epub 2020 Jul 22. — View Citation

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Polgreen PM, Chen YY, Cavanaugh JE, Ward M, Coffman S, Hornick DB, Diekema DJ, Herwaldt LA. An outbreak of severe Clostridium difficile-associated disease possibly related to inappropriate antimicrobial therapy for community-acquired pneumonia. Infect Control Hosp Epidemiol. 2007 Feb;28(2):212-4. doi: 10.1086/512174. Epub 2007 Jan 25. — View Citation

Rawson TM, Moore LSP, Zhu N, Ranganathan N, Skolimowska K, Gilchrist M, Satta G, Cooke G, Holmes A. Bacterial and Fungal Coinfection in Individuals With Coronavirus: A Rapid Review To Support COVID-19 Antimicrobial Prescribing. Clin Infect Dis. 2020 Dec 3;71(9):2459-2468. doi: 10.1093/cid/ciaa530. — View Citation

Sapp JL, Alqarawi W, MacIntyre CJ, Tadros R, Steinberg C, Roberts JD, Laksman Z, Healey JS, Krahn AD. Guidance on Minimizing Risk of Drug-Induced Ventricular Arrhythmia During Treatment of COVID-19: A Statement from the Canadian Heart Rhythm Society. Can J Cardiol. 2020 Jun;36(6):948-951. doi: 10.1016/j.cjca.2020.04.003. Epub 2020 Apr 8. — View Citation

Shah NS, Greenberg JA, McNulty MC, Gregg KS, Riddell J 4th, Mangino JE, Weber DM, Hebert CL, Marzec NS, Barron MA, Chaparro-Rojas F, Restrepo A, Hemmige V, Prasidthrathsint K, Cobb S, Herwaldt L, Raabe V, Cannavino CR, Hines AG, Bares SH, Antiporta PB, Scardina T, Patel U, Reid G, Mohazabnia P, Kachhdiya S, Le BM, Park CJ, Ostrowsky B, Robicsek A, Smith BA, Schied J, Bhatti MM, Mayer S, Sikka M, Murphy-Aguilu I, Patwari P, Abeles SR, Torriani FJ, Abbas Z, Toya S, Doktor K, Chakrabarti A, Doblecki-Lewis S, Looney DJ, David MZ. Bacterial and viral co-infections complicating severe influenza: Incidence and impact among 507 U.S. patients, 2013-14. J Clin Virol. 2016 Jul;80:12-9. doi: 10.1016/j.jcv.2016.04.008. Epub 2016 Apr 14. — View Citation

Stevens MP, Patel PK, Nori P. Involving antimicrobial stewardship programs in COVID-19 response efforts: All hands on deck. Infect Control Hosp Epidemiol. 2020 Jun;41(6):744-745. doi: 10.1017/ice.2020.69. No abstract available. — View Citation

Wan S, Xiang Y, Fang W, Zheng Y, Li B, Hu Y, Lang C, Huang D, Sun Q, Xiong Y, Huang X, Lv J, Luo Y, Shen L, Yang H, Huang G, Yang R. Clinical features and treatment of COVID-19 patients in northeast Chongqing. J Med Virol. 2020 Jul;92(7):797-806. doi: 10.1002/jmv.25783. Epub 2020 Apr 1. — View Citation

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. Erratum In: JAMA. 2021 Mar 16;325(11):1113. — View Citation

Wang Z, Yang B, Li Q, Wen L, Zhang R. Clinical Features of 69 Cases With Coronavirus Disease 2019 in Wuhan, China. Clin Infect Dis. 2020 Jul 28;71(15):769-777. doi: 10.1093/cid/ciaa272. — View Citation

Zhao XY, Xu XX, Yin HS, Hu QM, Xiong T, Tang YY, Yang AY, Yu BP, Huang ZP. Clinical characteristics of patients with 2019 coronavirus disease in a non-Wuhan area of Hubei Province, China: a retrospective study. BMC Infect Dis. 2020 Apr 29;20(1):311. doi: 10.1186/s12879-020-05010-w. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ordinal scale	A 7 point ordinal scale of clinical outcomes: point - Not hospitalized, able to resume normal daily activities; points - Not hospitalized, unable to resume normal daily activities; points - Hospitalized, not on supplemental oxygen; points - Hospitalized, on supplemental oxygen; points - Hospitalized, on high flow oxygen therapy or non-invasive mechanical ventilation; points - Hospitalized, on ECMO or invasive mechanical ventilation; points - Death; Higher scores means a worse outcome.	Day 15 of hospital admission
Secondary	Length of hospital stay	Duration of hospitalization in days	through study completion, an average of 5 days
Secondary	In-hospital mortality	Death occurring during hospital admission	through study completion, an average of 5 days
Secondary	30-day mortality	Mortality in the first 30 days after diagnosis	30 days
Secondary	30-day C. difficile associated mortality	Death related to C. difficile-associated diarrhea in the first 30 days after diagnosis	30 days
Secondary	30 day re-admission rate	Re-admission to hospital after initial discharge in the first 30 days after diagnosis	30 days from hospital discharge
Secondary	Days of therapy normalized for patient-days	Days of antibiotic therapy normalized for patients-day	capped at 30 days of hospitalization
Secondary	Length of total antimicrobial therapy normalized for patient-days	Length of antibiotics normalized for patient-days	capped at 30 days of hospitalization
Secondary	Number of antimicrobial stewardship audits	Number of audits by ASP	through study completion, an average of 5 days
Secondary	Number of antimicrobial stewardship recommendations	Number of recommendations by ASP	through study completion, an average of 5 days
Secondary	Antimicrobial stewardship acceptance rates	Acceptance rate of ASP recommendations	through study completion, an average of 5 days
Secondary	Multi-drug resistant bacteria infection rates	Development of multi-drug resistant bacterial infection in the first 30 days after diagnosis	30 days
Secondary	Clostridioides difficile infection rate	C. difficile-associated diarrhea in the first 30 days after diagnosis	30 days
Secondary	Percentage of participants with neutropenia	Occurrence of neutropenia in the first 30 days	30 days
Secondary	Acute kidney injury	diagnosed and staged as according to KDIGO	30 days