Bone and Joint Infection, Endovascular Infection, Gastrointestinal Infection, Genitourinary Infection, Pulmonary Infection, Skin and Soft Tissue Infection
Conditions
Keywords
COpAT, Oral antimicrobial therapy, OPAT, Parenteral antimicrobial therapy, Intravenous antimicrobial therapy, Implementation science
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.
Interventions
DRUGAmoxicillin, amoxicillin-clavulanate, cefadroxil, cefpodoxime, cefalexin, ciprofloxacin, delafloxacin, doxycycline, levofloxacin, linezolid
COpAT (oral antimicrobial therapy) on hospital discharge
DRUGAmpicillin, ampicillin-sulbactam, cefazolin, cefepime, ceftaroline, ceftazidime, ceftazidime-avibactam, dalbavancin, daptomycin, ertapenem
Standard of care (IV antimicrobial therapy) on hospital discharge
Sponsors
West Virginia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cure/Control at 3 Months | 3 months after hospital discharge | 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 |
| Adverse Events Related to Antimicrobial Therapy | Up to 3 months after hospital discharge | Number of participants with adverse events requiring intervention related to antimicrobial therapy (e.g., thrombocytopenia) |
| Adverse Events Related to Vascular Access | Up to 3 months after hospital discharge | Number of participants with adverse events requiring intervention related to vascular access complication (e.g., deep venous thrombosis) |
| Overall Readmission | Up to 3 months after hospital discharge | Number of participants readmitted for any reason up to 3 months after discharge from the hospital |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting 'Satisfied' or 'Very Satisfied' on Patient Satisfaction Survey | 6 weeks after hospital discharge | Patient satisfaction using the COPAT Trial Patient Satisfaction Survey at 6 Weeks, which is a short questionnaire (with the overall satisfaction question incorporating a Likert scale 1= Very Dissatisfied, 5= Very Satisfied) designed to assess overall patient satisfaction. Overall satisfaction totaled from participants answering 4= Satisfied and 5= Very Satisfied. |
| 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 | The number of participants who expressed a preference to be in the other study arm (i.e., answers 'Yes' to the survey question Would you have preferred to be in the other study arm? Yes or No). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1 (Experimental) COpAT (oral antimicrobial therapy) on hospital discharge
Amoxicillin, amoxicillin-clavulanate, cefadroxil, cefpodoxime, cefalexin, ciprofloxacin, delafloxacin, doxycycline, levofloxacin, linezolid: COpAT (oral antimicrobial therapy) on hospital discharge | 62 |
| Group 2 (Control) Standard of care (IV 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 | 28 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Transitioned to comfort care | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Group 2 (Control) | Total | Group 1 (Experimental) |
|---|---|---|---|
| Age, Continuous | 61.5 years | 60 years | 57.5 years |
| Bacteremia | 13 Participants | 43 Participants | 30 Participants |
| Comorbidities Cardiac | 13 participants | 31 participants | 18 participants |
| Comorbidities Diabetes | 11 participants | 44 participants | 33 participants |
| Comorbidities Obesity | 17 participants | 56 participants | 39 participants |
| Comorbidities Pulmonary | 5 participants | 15 participants | 10 participants |
| Comorbidities Renal | 0 participants | 6 participants | 6 participants |
| Infection Type Bone and Joint | 20 Participants | 66 Participants | 46 Participants |
| Infection Type Endovascular | 5 Participants | 13 Participants | 8 Participants |
| Infection Type Other | 3 Participants | 11 Participants | 8 Participants |
| Length of Hospital Stay | 10 days | 9 days | 8 days |
| Organism Isolated Enterobacterales | 3 participants | 11 participants | 8 participants |
| Organism Isolated MRSA | 3 participants | 18 participants | 15 participants |
| Organism Isolated MSSA | 14 participants | 37 participants | 23 participants |
| Organism Isolated Staphylococcus aureus | 17 participants | 55 participants | 38 participants |
| Organism Isolated Streptococcus species | 7 participants | 20 participants | 13 participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 28 participants | 90 participants | 62 participants |
| Sex: Female, Male Female | 8 Participants | 33 Participants | 25 Participants |
| Sex: Female, Male Male | 20 Participants | 57 Participants | 37 Participants |
| Surgery/Drainage | 19 Participants | 74 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 64 | 0 / 30 |
| other Total, other adverse events | 4 / 64 | 8 / 30 |
| serious Total, serious adverse events | 18 / 64 | 7 / 30 |
Outcome results
Primary
Adverse Events Related to Antimicrobial Therapy
Number of participants with adverse events requiring intervention related to antimicrobial therapy (e.g., thrombocytopenia)
Time frame: Up to 3 months after hospital discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Experimental) | Adverse Events Related to Antimicrobial Therapy | 4 Participants |
| Group 2 (Control) | Adverse Events Related to Antimicrobial Therapy | 4 Participants |
Primary
Adverse Events Related to Vascular Access
Number of participants with adverse events requiring intervention related to vascular access complication (e.g., deep venous thrombosis)
Time frame: Up to 3 months after hospital discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Experimental) | Adverse Events Related to Vascular Access | 0 Participants |
| Group 2 (Control) | Adverse Events Related to Vascular Access | 7 Participants |
Primary
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
Time frame: 3 months after hospital discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Experimental) | Cure/Control at 3 Months | 61 Participants |
| Group 2 (Control) | Cure/Control at 3 Months | 28 Participants |
Primary
Overall Readmission
Number of participants readmitted for any reason up to 3 months after discharge from the hospital
Time frame: Up to 3 months after hospital discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group 1 (Experimental) | Overall Readmission | 17 Participants |
| Group 2 (Control) | Overall Readmission | 7 Participants |
Secondary
Number of Participants Reporting 'Satisfied' or 'Very Satisfied' on Patient Satisfaction Survey
Patient satisfaction using the COPAT Trial Patient Satisfaction Survey at 6 Weeks, which is a short questionnaire (with the overall satisfaction question incorporating a Likert scale 1= Very Dissatisfied, 5= Very Satisfied) designed to assess overall patient satisfaction. Overall satisfaction totaled from participants answering 4= Satisfied and 5= Very Satisfied.
Time frame: 6 weeks after hospital discharge
Population: Four withdrew early prior to hospital discharge: 3 chose not to participate, and one transitioned to comfort care (mortality).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Experimental) | Number of Participants Reporting 'Satisfied' or 'Very Satisfied' on Patient Satisfaction Survey | 60 participants |
| Group 2 (Control) | Number of Participants Reporting 'Satisfied' or 'Very Satisfied' on Patient Satisfaction Survey | 27 participants |
Secondary
Number of Participants Who Answered 'Yes' to the Survey Question Would You Have Preferred to be in the Other Study Arm? (Yes or No)
The number of participants who expressed a preference to be in the other study arm (i.e., answers 'Yes' to the survey question Would you have preferred to be in the other study arm? Yes or No).
Time frame: 6 weeks after hospital discharge
Population: Four withdrew early prior to hospital discharge: three chose not to participate, and one transitioned to comfort care (mortality).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 (Experimental) | Number of Participants Who Answered 'Yes' to the Survey Question Would You Have Preferred to be in the Other Study Arm? (Yes or No) | 1 participants |
| Group 2 (Control) | Number of Participants Who Answered 'Yes' to the Survey Question Would You Have Preferred to be in the Other Study Arm? (Yes or No) | 21 participants |