Postoperative Antibiotic Management Duration Following Surgery for Intravenous Drug Abuse (IVDA) Endocarditis (OPTIMAL)

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and compliance of initial intravenous (IV) antibiotics followed by oral antibiotic therapy following uncomplicated IVDA endocarditis. Endocarditis has a high rate of sickness and death, involves a long hospitalization and a long-term use of IV antibiotics necessitating six (6) weeks of in-patient hospital stay, and comes with a high cost.

Official Title
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Postoperative Antibiotic Management Duration Following Surgery for Intravenous Drug Abuse (IVDA) Endocarditis (OPTIMAL)

Conditions
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Endocarditis

Intervention / Treatment
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* Drug: Amoxycillin, Cefalexin, Dicloxacillin, Linezolid, Levofloxacin, Rifampicin
* Drug: Ampicillin, Oxacillin, Vancomycin, Daptomycin, Ceftriaxone, Cefepime, Ceftaroline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The age of the patient is ≥ 18. The patient has undergone an urgent or emergent primary cardiac valvar operation as treatment for IVDA endocarditis, with blood cultures positive for Streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative Staphylococci The patient has received 2 weeks of postoperative inpatient IV antibiotic therapy with negative blood cultures and no residual active infection by imaging (i.e. computerized axial tomography, echocardiography) The patient has the capacity to participate in a compliance tracking tool for medication administration (e.g. a centrally managed core site mobile Medisafe compliance https://www.medisafe.com/) as confirmed by both a physician and a care management team member Exclusion Criteria: Inability to give informed consent Residual infection requiring IV antibiotic therapy Any persistent secondary noncardiac infection (e.g. infections of solid organs or joints) Known poor compliance or deemed incapable to comply with the compliance tracking tool Reduced absorption or inability to receive oral treatment due to a gastrointestinal disorder Any infection involving a more virulent organisms, such as fungal infections or infections with Serratia or HACEK infections (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella). Cancer not otherwise in remission or in need of current or future oncologic therapy Medically immunocompromised state Reoperative valvar operation for IVDA endocarditis History of habitual noncompliance Pregnancy Mental incapacity Unable to perform local or institutional medical and psychiatric follow up Unstable home environment Inadequate access to mobile cell service (geographic/rurality)

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
Interventional Model Description: Postoperative patients who have undergone valvar repair or replacement for IVDA endocarditis will be randomized into two arms: Experimental: 2 weeks of postoperative inpatient IV antibiotic therapy followed by 4 weeks of oral therapy with outpatient follow-up; Control: conventional 2 weeks of postoperative inpatient IV antibiotic therapy followed by 4 weeks of IV antibiotic therapy (inpatient or facility supervised if indwelling catheter utilized). Both groups will receive aggressive drug rehabilitation with mandatory participation in a formal psychiatric rehabilitation program for a minimum of 6 weeks (combined inpatient and outpatient), will be followed by Infectious Disease, will undergo monitoring of treatment efficacy with serum antibiotic levels, will undergo surveillance monitoring of treatment efficacy with blood cultures, will participate in a compliance tracking tool for medication administration (e.g. a centrally managed core site mobile Medisafe compliance program.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (Experimental)<br>Two (2) weeks of postoperative inpatient IV antibiotic therapy followed by four (4) weeks of oral therapy with outpatient follow-up. | Drug: Amoxycillin, Cefalexin, Dicloxacillin, Linezolid, Levofloxacin, Rifampicin<br>* Amoxycillin, Cefalexin, Dicloxacillin, Linezolid, Levofloxacin, Rifampicin<br>Drug: Ampicillin, Oxacillin, Vancomycin, Daptomycin, Ceftriaxone, Cefepime, Ceftaroline<br>* Ampicillin, Oxacillin, Vancomycin, Daptomycin, Ceftriaxone, Cefepime, Ceftaroline<br>|
| Active Comparator: Group II (Control Group)<br>Conventional two (2) weeks of postoperative inpatient IV antibiotic therapy followed by four (4) weeks of IV antibiotic therapy (inpatient or facility supervised if indwelling catheter utilized). | Drug: Ampicillin, Oxacillin, Vancomycin, Daptomycin, Ceftriaxone, Cefepime, Ceftaroline<br>* Ampicillin, Oxacillin, Vancomycin, Daptomycin, Ceftriaxone, Cefepime, Ceftaroline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess all-cause mortality at six (6) months post-surgery. | To assess all-cause mortality at six (6) months post-surgery. | Six months | 
| To assess all-cause mortality at (12) months post-surgery. | To assess all-cause mortality at (12) months post-surgery. | One year | 
| To assess recurrent blood culture positive infection. | To assess recurrent blood culture positive infection. | Six months | 
| To assess recurrent blood culture positive infection. | To assess recurrent blood culture positive infection. | One year | 
| To assess cardiac re-operation. | To assess cardiac re-operation. | Six months | 
| To assess cardiac re-operation. | To assess cardiac re-operation. | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Readmission for recurrent infection or cardiac re-operation | Readmission for recurrent infection or cardiac re-operation | Six months | 
| Readmission for recurrent infection or cardiac re-operation | Readmission for recurrent infection or cardiac re-operation | One year | 
| Cost of care | Cost of care | Through study completion, an average of one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intravenous Drug Abuse Endocarditis, Oral Antibiotics, IV Antibiotics