Clinical trial NCT05156437: Postoperative Antibiotic Management Duration Following Surgery for Intravenous Drug Abuse (IVDA) Endocarditis (OPTIMAL)
Official title: Postoperative Antibiotic Management Duration Following Surgery for Intravenous Drug Abuse (IVDA) Endocarditis (OPTIMAL)
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE4
Conditions: Endocarditis
Keywords: Intravenous Drug Abuse Endocarditis
Oral Antibiotics
IV Antibiotics
Lead sponsor: West Virginia University
Sponsor class: OTHER
First posted: 2021-12-14
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: To assess all-cause mortality at six (6) months post-surgery.
timeFrame: Six months
measure: To assess all-cause mortality at (12) months post-surgery.
timeFrame: One year
measure: To assess recurrent blood culture positive infection.
timeFrame: Six months
measure: To assess recurrent blood culture positive infection.
timeFrame: One year
measure: To assess cardiac re-operation.
timeFrame: Six months
measure: To assess cardiac re-operation.
timeFrame: One year
Secondary outcomes:
measure: Readmission for recurrent infection or cardiac re-operation
timeFrame: Six months
measure: Readmission for recurrent infection or cardiac re-operation
timeFrame: One year
measure: Cost of care
timeFrame: Through study completion, an average of one year
Other outcomes:
Locations:
city: Morgantown
country: United States
facility: WVU Heart and Vascular Institute
state: West Virginia
Study officials:
affiliation: West Virginia University
name: Vinay Badhwar, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: Spellberg B, Chambers HF, Musher DM, Walsh TL, Bayer AS. Evaluation of a Paradigm Shift From Intravenous Antibiotics to Oral Step-Down Therapy for the Treatment of Infective Endocarditis: A Narrative Review. JAMA Intern Med. 2020 May 1;180(5):769-777. doi: 10.1001/jamainternmed.2020.0555.
citation: Lemaignen A, Bernard L, Tattevin P, Bru JP, Duval X, Hoen B, Brunet-Houdard S, Mainardi JL, Caille A; RODEO (Relais Oral Dans le traitement des Endocardites a staphylocoques ou streptOcoques) and AEPEI (Association pour l'Etude et la Prevention de l'Endocardite Infectieuse) study groups. Oral switch versus standard intravenous antibiotic therapy in left-sided endocarditis due to susceptible staphylococci, streptococci or enterococci (RODEO): a protocol for two open-label randomised controlled trials. BMJ Open. 2020 Jul 14;10(7):e033540. doi: 10.1136/bmjopen-2019-033540.
citation: Brown E, Gould FK. Oral antibiotics for infective endocarditis: a clinical review. J Antimicrob Chemother. 2020 Aug 1;75(8):2021-2027. doi: 10.1093/jac/dkaa106.
citation: Scholl L, Seth P, Kariisa M, Wilson N, Baldwin G. Drug and Opioid-Involved Overdose Deaths - United States, 2013-2017. MMWR Morb Mortal Wkly Rep. 2018 Jan 4;67(5152):1419-1427. doi: 10.15585/mmwr.mm675152e1.
citation: Wurcel AG, Anderson JE, Chui KK, Skinner S, Knox TA, Snydman DR, Stopka TJ. Increasing Infectious Endocarditis Admissions Among Young People Who Inject Drugs. Open Forum Infect Dis. 2016 Jul 26;3(3):ofw157. doi: 10.1093/ofid/ofw157. eCollection 2016 Sep.
citation: Kornbau C, Lee KC, Hughes GD, Firstenberg MS. Central line complications. Int J Crit Illn Inj Sci. 2015 Jul-Sep;5(3):170-8. doi: 10.4103/2229-5151.164940.
citation: Badhwar V, Wei LM, Rankin JS. Seeing the entire forest in endocarditis. J Thorac Cardiovasc Surg. 2016 Sep;152(3):681-2. doi: 10.1016/j.jtcvs.2016.05.050. Epub 2016 Jun 4. No abstract available.