Clinical trial NCT05977868: Comparing Oral Versus Parenteral Antimicrobial Therapy
Official title: Comparing Oral Versus Parenteral Antimicrobial Therapy (COPAT) Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Endovascular Infection
Bone and Joint Infection
Skin and Soft Tissue Infection
Pulmonary Infection
Gastrointestinal Infection
Genitourinary Infection
Keywords: COpAT
Oral antimicrobial therapy
OPAT
Parenteral antimicrobial therapy
Intravenous antimicrobial therapy
Lead sponsor: West Virginia University
Sponsor class: OTHER
First posted: 2023-08-07
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an investigator initiated multisite pragmatic randomized controlled trial designed to demonstrate equivalent effectiveness with improved safety of early transition from intravenous (IV) antimicrobial therapy to complex outpatient oral antimicrobial therapy (COpAT) across various infectious diseases (endovascular, bone and joint, skin and soft tissue, pulmonary, gastrointestinal, and genitourinary infections).

All patients referred for outpatient parenteral antimicrobial therapy (OPAT) will be evaluated by the research team with respect to inclusion/exclusion criteria. If determined eligible for enrollment, patients will be approached by a study investigator who will present the COPAT Trial. Once informed consent is obtained, patients will be randomized 2:1 using computer software into experimental or control (standard of care) group, respectively: Experimental: COpAT only on hospital discharge; Control: Conventional OPAT, OPAT transitioned to COpAT later in outpatient setting, or long-acting parenteral lipoglycopeptides. Both groups will be followed by an ID physician on the research team with in-person or telemedicine ID Clinic standard of care visits at 2, 6, and 12 weeks after hospital discharge. At the 6-week ID Clinic follow-up, patients will be asked to complete a patient satisfaction survey. The following 2 primary outcomes will be assessed: cure at 3 months using clinical (resolution of infection) and laboratory parameters (improvement in inflammatory markers) and adverse events related to antimicrobial therapy/vascular access complication. The following 3 secondary outcomes will be assessed: overall readmission at 3 months, readmission related to initial infection or antimicrobial therapy/vascular access complication at 3 months, and patient satisfaction at 6 weeks. The experimental group is being compared to standard of care in current clinical practice.

As this is a pragmatic clinical trial, patients will not undergo additional invasive testing or procedures.


Eligibility criteria: Inclusion (must meet all of the following):

* English speaking
* The patient is hospitalized at J.W. Ruby Memorial Hospital, United Hospital Center, Berkeley Medical Center, Wheeling Hospital, or Camden Clark Medical Center
* The patient has been diagnosed with ≥1 of the following: endovascular, bone and joint, skin and soft tissue, pulmonary, gastrointestinal, or genitourinary infection
* The patient is being transitioned to 2-8 weeks of IV antibacterial therapy on hospital discharge
* The patient has capacity to participate in routine OPAT/COpAT follow-up (telephone check-ins, laboratory monitoring, and in-person or telemedicine ID Clinic follow-up)

Exclusion (may not meet any of the following):

* The patient is not appropriate for OPAT (active injection drug use, lack of infusion resources, and/or unstable outpatient environment)
* The patient is not appropriate for COpAT (unable to receive PO medication or lack of an effective PO antimicrobial option based on susceptibility testing)
* The patient is unable to give informed consent
* The patient is a prisoner, pregnant, and/or mentally handicapped
* The patient is determined unsafe for enrollment at the primary team's discretion

Primary outcomes:
measure: Cure at 3 months
timeFrame: 3 months after hospital discharge
measure: Adverse events related to antimicrobial therapy/vascular access complication
timeFrame: Up to 3 months after hospital discharge
Secondary outcomes:
measure: Overall readmission at 3 months
timeFrame: Up to 3 months after hospital discharge
measure: Readmission related to initial infection or antimicrobial therapy/vascular access complication at 3 months
timeFrame: Up to 3 months after hospital discharge
measure: Patient satisfaction
timeFrame: 6 weeks after hospital discharge
Other outcomes:
Locations:
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
Study officials:
affiliation: West Virginia University
name: Joy J. Juskowich, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: West Virginia University
name: Arif R. Sarwari, MD, MSc, MBA
role: PRINCIPAL_INVESTIGATOR
References:
citation: Iversen K, Ihlemann N, Gill SU, Madsen T, Elming H, Jensen KT, Bruun NE, Hofsten DE, Fursted K, Christensen JJ, Schultz M, Klein CF, Fosboll EL, Rosenvinge F, Schonheyder HC, Kober L, Torp-Pedersen C, Helweg-Larsen J, Tonder N, Moser C, Bundgaard H. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2019 Jan 31;380(5):415-424. doi: 10.1056/NEJMoa1808312. Epub 2018 Aug 28.
citation: Li HK, Rombach I, Zambellas R, Walker AS, McNally MA, Atkins BL, Lipsky BA, Hughes HC, Bose D, Kumin M, Scarborough C, Matthews PC, Brent AJ, Lomas J, Gundle R, Rogers M, Taylor A, Angus B, Byren I, Berendt AR, Warren S, Fitzgerald FE, Mack DJF, Hopkins S, Folb J, Reynolds HE, Moore E, Marshall J, Jenkins N, Moran CE, Woodhouse AF, Stafford S, Seaton RA, Vallance C, Hemsley CJ, Bisnauthsing K, Sandoe JAT, Aggarwal I, Ellis SC, Bunn DJ, Sutherland RK, Barlow G, Cooper C, Geue C, McMeekin N, Briggs AH, Sendi P, Khatamzas E, Wangrangsimakul T, Wong THN, Barrett LK, Alvand A, Old CF, Bostock J, Paul J, Cooke G, Thwaites GE, Bejon P, Scarborough M; OVIVA Trial Collaborators. Oral versus Intravenous Antibiotics for Bone and Joint Infection. N Engl J Med. 2019 Jan 31;380(5):425-436. doi: 10.1056/NEJMoa1710926.
citation: Pries-Heje MM, Wiingaard C, Ihlemann N, Gill SU, Bruun NE, Elming H, Povlsen JA, Madsen T, Jensen KT, Fursted K, Schultz M, Ostergaard L, Christensen JJ, Christiansen U, Rosenvinge F, Helweg-Larsen J, Fosbol EL, Kober L, Torp-Pedersen C, Tonder N, Moser C, Iversen K, Bundgaard H. Five-Year Outcomes of the Partial Oral Treatment of Endocarditis (POET) Trial. N Engl J Med. 2022 Feb 10;386(6):601-602. doi: 10.1056/NEJMc2114046. No abstract available.
citation: Staples JA, Ho M, Ferris D, Hayek J, Liu G, Tran KC, Sutherland JM. Outpatient Versus Inpatient Intravenous Antimicrobial Therapy: A Population-Based Observational Cohort Study of Adverse Events and Costs. Clin Infect Dis. 2022 Nov 30;75(11):1921-1929. doi: 10.1093/cid/ciac298.
citation: Rivera CG, Mehta M, Ryan KL, Stevens RW, Tucker KJ, Mahoney MV. Role of infectious diseases pharmacists in outpatient intravenous and complex oral antimicrobial therapy: Society of Infectious Diseases Pharmacists insights. J Am Coll Clin Pharm. 2021;4:1161-1169. doi: 10.1002/jac5.1473
citation: Juskowich JJ, Ward A, Spigelmyer AE, Howard CA, Slain D, Guilfoose JA, Edmond MB, Sarwari AR. Complex Outpatient Oral Antimicrobial Therapy (COpAT) Program at a Rural Academic Medical Center: Evaluation of First 100 Patients. Open Forum Infect Dis. 2022; 9(2): S418-S419. doi: 10.1093/ofid/ofac492.843
citation: Freling S, Wald-Dickler N, Banerjee J, Canamar CP, Tangpraphaphorn S, Bruce D, Davar K, Dominguez F, Norwitz D, Krishnamurthi G, Fung L, Guanzon A, Minejima E, Spellberg M, Spellberg C, Baden R, Holtom P, Spellberg B. Real-World Application of Oral Therapy for Infective Endocarditis: A Multicenter, Retrospective, Cohort Study. Clin Infect Dis. 2023 Sep 11;77(5):672-679. doi: 10.1093/cid/ciad119.