Comparing Oral Versus Parenteral Antimicrobial Therapy (COPAT)

• ClinicalTrials.gov Identifier: NCT05977868
• Recruitment Status: Enrolling by invitation
• First Posted: August 7, 2023
• Last Update Posted: December 12, 2023
• Sponsor: West Virginia University
• Information provided by (Responsible Party): Joy J. Juskowich, MD, West Virginia University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Endovascular Infection; Bone and Joint Infection; Skin and Soft Tissue Infection; Pulmonary Infection; Gastrointestinal Infection; Genitourinary Infection	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	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 135 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: The primary outcome of cure at 3 months will be adjudicated by a 2 ID faculty blinded to study arm.
• Primary Purpose: Treatment
• Official Title: Comparing Oral Versus Parenteral Antimicrobial Therapy (COPAT) Trial
• Actual Study Start Date: August 4, 2023
• Estimated Primary Completion Date: August 2024
• Estimated Study Completion Date: August 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Cure at 3 months [ Time Frame: 3 months after hospital discharge ]
   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
2. Adverse events related to antimicrobial therapy/vascular access complication [ Time Frame: Up to 3 months after hospital discharge ]
   Number of adverse events requiring intervention related to antimicrobial therapy (e.g., thrombocytopenia) and/or vascular access complication (e.g., deep venous thrombosis)

Secondary Outcome Measures :

1. Overall readmission at 3 months [ Time Frame: Up to 3 months after hospital discharge ]
   Number of patients readmitted for any reason
2. Readmission related to initial infection or antimicrobial therapy/vascular access complication at 3 months [ Time Frame: Up to 3 months after hospital discharge ]
   Number of patients readmitted for a reason related to initial infection or antimicrobial therapy/vascular access complication
3. Patient satisfaction [ Time Frame: 6 weeks after hospital discharge ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, West Virginia

West Virginia University

Morgantown, West Virginia, United States, 26506

Sponsors and Collaborators

West Virginia University

Investigators

• Principal Investigator: Joy J. Juskowich, MD; West Virginia University
• Principal Investigator: Arif R. Sarwari, MD, MSc, MBA; West Virginia University

More Information

Publications:

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.

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.

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.

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.

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

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

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.

• Responsible Party: Joy J. Juskowich, MD, Assistant Professor, West Virginia University
• ClinicalTrials.gov Identifier: NCT05977868
• Other Study ID Numbers: 2304754420
• First Posted: August 7, 2023
• Last Update Posted: December 12, 2023
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Joy J. Juskowich, MD, West Virginia University:

COpAT; Oral antimicrobial therapy; OPAT; Parenteral antimicrobial therapy; Intravenous antimicrobial therapy

Additional relevant MeSH terms:

Infections; Communicable Diseases; Soft Tissue Infections; Disease Attributes; Pathologic Processes; Amoxicillin; Moxifloxacin; Metronidazole; Vancomycin; Doxycycline; Levofloxacin; Ciprofloxacin; Rifampin; Meropenem; Cefazolin; Tazobactam; Linezolid; Piperacillin; Clavulanic Acid; Penicillins; Daptomycin; Ceftazidime; Cephalexin; Ampicillin; Cefepime; Ertapenem; Ceftaroline; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination; Piperacillin, Tazobactam Drug Combination