Comparing Oral Versus Parenteral Antimicrobial Therapy

NCT05977868 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: 2304754420
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

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 (improvement in inflammatory markers) parameters and adverse events related to antimicrobial therapy/vascular access complication or readmission at 3 months. The following secondary outcome will be assessed: 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.

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; Implementation science

Outcome Measures

Primary Outcomes (4)

• Cure/Control at 3 Months

  Number of patients with cure/control 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

  Number of participants with adverse events requiring intervention related to antimicrobial therapy (e.g., thrombocytopenia)

  Up to 3 months after hospital discharge

• Adverse Events Related to Vascular Access

  Number of participants with adverse events requiring intervention related to vascular access complication (e.g., deep venous thrombosis)

  Up to 3 months after hospital discharge

• Overall Readmission

  Number of participants readmitted for any reason up to 3 months after discharge from the hospital

  Up to 3 months after hospital discharge

Secondary Outcomes (2)

• Number of Participants Reporting 'Satisfied' or 'Very Satisfied' on Patient Satisfaction Survey

  6 weeks after hospital discharge

• Number of Participants Who Answered 'Yes' to the Survey Question "Would You Have Preferred to be in the Other Study Arm? (Yes or No)"

  6 weeks after hospital discharge

Study Arms (2)

Group 1 (Experimental)

EXPERIMENTAL

COpAT (oral antimicrobial therapy) on hospital discharge

Drug: Amoxicillin, amoxicillin-clavulanate, cefadroxil, cefpodoxime, cefalexin, ciprofloxacin, delafloxacin, doxycycline, levofloxacin, linezolid

Group 2 (Control)

ACTIVE COMPARATOR

Standard of care (IV antimicrobial therapy) on hospital discharge

Drug: Ampicillin, ampicillin-sulbactam, cefazolin, cefepime, ceftaroline, ceftazidime, ceftazidime-avibactam, dalbavancin, daptomycin, ertapenem

Interventions

Amoxicillin, amoxicillin-clavulanate, cefadroxil, cefpodoxime, cefalexin, ciprofloxacin, delafloxacin, doxycycline, levofloxacin, linezolid DRUG

COpAT (oral antimicrobial therapy) on hospital discharge

Also known as: metronidazole, moxifloxacin, rifampin, trimethoprim-sulfamethoxazole

Group 1 (Experimental)

Ampicillin, ampicillin-sulbactam, cefazolin, cefepime, ceftaroline, ceftazidime, ceftazidime-avibactam, dalbavancin, daptomycin, ertapenem DRUG

Standard of care (IV antimicrobial therapy) on hospital discharge

Also known as: meropenem, oritavancin, oxacillin, penicillin, piperacillin-tazobactam, tigecycline, vancomycin

Group 2 (Control)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• West Virginia University: lead

Study Sites (1)

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Related Publications (7)

• 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.

  PMID: 30152252 BACKGROUND

• 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.

  PMID: 30699315 BACKGROUND

• 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.

  PMID: 35139280 BACKGROUND

• 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.

  PMID: 35439822 BACKGROUND

• 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

  BACKGROUND

• 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

  BACKGROUND

• 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.

  PMID: 36881940 BACKGROUND

MeSH Terms

Conditions

Soft Tissue Infections

Interventions

Amoxicillin; Amoxicillin-Potassium Clavulanate Combination; Cefadroxil; Cefpodoxime; Cephalexin; Ciprofloxacin; delafloxacin; Doxycycline; Levofloxacin; Linezolid; Metronidazole; Moxifloxacin; Rifampin; Trimethoprim, Sulfamethoxazole Drug Combination; Ampicillin; sultamicillin; Cefazolin; Cefepime; Ceftaroline; Ceftazidime; avibactam, ceftazidime drug combination; dalbavancin; Daptomycin; Ertapenem; Meropenem; oritavancin; Oxacillin; Penicillins; Piperacillin, Tazobactam Drug Combination; Tigecycline; Vancomycin

Condition Hierarchy (Ancestors)

Infections

Intervention Hierarchy (Ancestors)

Penicillin G; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Clavulanic Acid; Clavulanic Acids; Drug Combinations; Pharmaceutical Preparations; Cephalosporins; Thiazines; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Ofloxacin; Acetamides; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Nitroimidazoles; Nitro Compounds; Imidazoles; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Sulfones; Trimethoprim; Pyrimidines; Cephaloridine; Peptides, Cyclic; Lipopeptides; Lipids; Peptides; Amino Acids, Peptides, and Proteins; Carbapenems; Thienamycins; Tazobactam; Penicillanic Acid; Piperacillin; Glycopeptides; Glycoconjugates; Carbohydrates

Limitations and Caveats

Our trial was unblinded for pragmatic reasons. Assessment of clinical cure/control by 2 ID physicians blinded to study arm minimized potential bias. More patients in Experimental group had a procedure for source control. At least two ID physicians select oral regimens to optimize safety. Patients with active SUD/IDU were excluded. All patients were followed through OPAT and COpAT programs. Study results may not be generalizable to institutions/practices without these programs.

Results Point of Contact

• Title: Dr. Joy J. Juskowich
• Organization: West Virginia University

jjuskowi@hsc.wvu.edu

304-293-3306

Study Officials

• Joy J. Juskowich, MD

  West Virginia University

  PRINCIPAL INVESTIGATOR

• Arif R. Sarwari, MD, MSc, MBA

  West Virginia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The primary outcome of cure at 3 months will be adjudicated by a 2 ID faculty blinded to study arm.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 14, 2023
• First Posted: August 7, 2023
• Study Start: August 4, 2023
• Primary Completion: February 14, 2025
• Study Completion: February 14, 2025
• Last Updated: August 26, 2025
• Results First Posted: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)