Comparing Oral Versus Parenteral Antimicrobial Therapy

Bone and Joint Infection Clinical Trial

— COPAT  

Official title:

Comparing Oral Versus Parenteral Antimicrobial Therapy (COPAT) Trial

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05977868
• Other study ID #: 2304754420
• Status: Enrolling by invitation
• Phase: Phase 4
• Start date: August 4, 2023
• Est. completion date: August 2024

Study information

• Verified date: December 2023
• Source: West Virginia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 135
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bone and Joint Infection
• Communicable Diseases
• Gastrointestinal Infection
• Infections
• Pulmonary Infection
• Skin and Soft Tissue Infection
• Soft Tissue Infections

Intervention

Drug:
• Amoxicillin, amoxicillin-clavulanate, cefadroxil, cefpodoxime, cefalexin, ciprofloxacin, delafloxacin, doxycycline, levofloxacin, linezolid
COpAT (oral antimicrobial therapy) on hospital discharge
• Ampicillin, ampicillin-sulbactam, cefazolin, cefepime, ceftaroline, ceftazidime, ceftazidime-avibactam, dalbavancin, daptomycin, ertapenem
Standard of care (IV antimicrobial therapy) on hospital discharge

Locations

Country	Name	City	State
United States	West Virginia University	Morgantown	West Virginia

Sponsors (1)

Lead Sponsor	Collaborator
West Virginia University

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View 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. — View 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

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. — View 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. — View 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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Overall readmission at 3 months	Number of patients readmitted for any reason	Up to 3 months after hospital discharge
Secondary	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
Secondary	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