Comparing Oral Versus Parenteral Antimicrobial Therapy

Study Overview
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Brief Summary
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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.

Official Title
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Comparing Oral Versus Parenteral Antimicrobial Therapy (COPAT) Trial

Conditions
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Endovascular Infection, Bone and Joint Infection, Skin and Soft Tissue Infection, Pulmonary Infection, Gastrointestinal Infection, Genitourinary Infection

Intervention / Treatment
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* Drug: Amoxicillin, amoxicillin-clavulanate, cefadroxil, cefpodoxime, cefalexin, ciprofloxacin, delafloxacin, doxycycline, levofloxacin, linezolid
* Drug: Ampicillin, ampicillin-sulbactam, cefazolin, cefepime, ceftaroline, ceftazidime, ceftazidime-avibactam, dalbavancin, daptomycin, ertapenem


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (Experimental)<br>COpAT (oral antimicrobial therapy) on hospital discharge | Drug: Amoxicillin, amoxicillin-clavulanate, cefadroxil, cefpodoxime, cefalexin, ciprofloxacin, delafloxacin, doxycycline, levofloxacin, linezolid<br>* COpAT (oral antimicrobial therapy) on hospital discharge<br>* Other names: metronidazole, moxifloxacin, rifampin, trimethoprim-sulfamethoxazole;|
| Active Comparator: Group 2 (Control)<br>Standard of care (IV antimicrobial therapy) on hospital discharge | Drug: Ampicillin, ampicillin-sulbactam, cefazolin, cefepime, ceftaroline, ceftazidime, ceftazidime-avibactam, dalbavancin, daptomycin, ertapenem<br>* Standard of care (IV antimicrobial therapy) on hospital discharge<br>* Other names: meropenem, oritavancin, oxacillin, penicillin, piperacillin-tazobactam, tigecycline, vancomycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cure at 3 months | Number of patients with cure using clinical (resolution of infection - e.g., wound healed) and laboratory (improvement in inflammatory markers - e.g., CRP normalization) parameters as adjudicated by 2 ID faculty blinded to study arm | 3 months after hospital discharge | 
| Adverse events related to antimicrobial therapy/vascular access complication | Number of adverse events requiring intervention related to antimicrobial therapy (e.g., thrombocytopenia) and/or vascular access complication (e.g., deep venous thrombosis) | Up to 3 months after hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall readmission at 3 months | Number of patients readmitted for any reason | Up to 3 months after hospital discharge | 
| Readmission related to initial infection or antimicrobial therapy/vascular access complication at 3 months | Number of patients readmitted for a reason related to initial infection or antimicrobial therapy/vascular access complication | Up to 3 months after hospital discharge | 
| Patient satisfaction | Patient satisfaction using the COPAT Trial Patient Satisfaction Survey at 6 Weeks, which is a short questionnaire (with some questions incorporating a Likert scale 0=worst, 5=best) designed to assess overall patient satisfaction | 6 weeks after hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COpAT, Oral antimicrobial therapy, OPAT, Parenteral antimicrobial therapy, Intravenous antimicrobial therapy