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

NCT05156437 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: 2109416021
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Endocarditis

Keywords

Intravenous Drug Abuse Endocarditis; Oral Antibiotics; IV Antibiotics

Outcome Measures

Primary Outcomes (6)

• All-cause Mortality at Six (6) Months Post-surgery.

  Incidences of all-cause mortality at six (6) months post-surgery.

  Six months

• All-cause Mortality at (12) Months Post-surgery.

  Incidences of all-cause mortality at (12) months post-surgery.

  One year

• Incidence of Recurrent Blood Culture Positive Infection (6 Month)

  Incidence of recurrent blood culture positive infection (6 month)

  Six months

• Incidence of Recurrent Blood Culture Positive Infection (1 Year)

  Incidence of recurrent blood culture positive infection (1 year)

  One year

• Incidence of Cardiac Re-operation (6 Month)

  Incidence of cardiac re-operation (6 Month)

  Six months

• Incidence of Cardiac Re-operation (1 Year)

  Incidence of cardiac re-operation (1 Year)

  One year

Secondary Outcomes (3)

• Readmission for Recurrent Infection or Cardiac Re-operation (6 Month)

  Six months

• Readmission for Recurrent Infection or Cardiac Re-operation (1 Year)

  One year

• Cost of Care

  Through study completion, an average of one year

Study Arms (2)

Group I (Experimental)

EXPERIMENTAL

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; Drug: Ampicillin, Oxacillin, Vancomycin, Daptomycin, Ceftriaxone, Cefepime, Ceftaroline

Group II (Control Group)

ACTIVE COMPARATOR

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

Interventions

Amoxycillin, Cefalexin, Dicloxacillin, Linezolid, Levofloxacin, Rifampicin DRUG

Amoxycillin, Cefalexin, Dicloxacillin, Linezolid, Levofloxacin, Rifampicin

Group I (Experimental)

Ampicillin, Oxacillin, Vancomycin, Daptomycin, Ceftriaxone, Cefepime, Ceftaroline DRUG

Ampicillin, Oxacillin, Vancomycin, Daptomycin, Ceftriaxone, Cefepime, Ceftaroline

Group I (Experimental); Group II (Control Group)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• West Virginia University: lead

Study Sites (1)

WVU Heart and Vascular Institute

Morgantown, West Virginia, 26506, United States

Location

Related Publications (8)

• 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

• 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.

  PMID: 32227127 BACKGROUND

• 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.

  PMID: 32665381 BACKGROUND

• 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.

  PMID: 32240296 BACKGROUND

• 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.

  PMID: 30605448 BACKGROUND

• 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.

  PMID: 27800528 BACKGROUND

• 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.

  PMID: 26557487 BACKGROUND

• 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.

  PMID: 27325495 BACKGROUND

Related Links

• Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER): Multiple cause of death 1999-2017

MeSH Terms

Conditions

Endocarditis

Interventions

Amoxicillin; Cephalexin; Dicloxacillin; Linezolid; Levofloxacin; Rifampin; Ampicillin; Oxacillin; Vancomycin; Daptomycin; Ceftriaxone; Cefepime; Ceftaroline

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cephalosporins; Thiazines; Cloxacillin; Acetamides; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Peptides, Cyclic; Lipopeptides; Lipids; Cefotaxime; Cephacetrile

Limitations and Caveats

This study had complete loss to follow-up for all enrolled participants (N=5), a vulnerable population with high instability due to substance use disorder. No participant completed treatment or any follow-up visit, so no outcome data were collected and no endpoints could be evaluated. The small sample and lack of data prevent statistical analysis and limit study conclusions.

Results Point of Contact

• Title: Dr. Vinay Badhwar
• Organization: West Virginia University

vinay.badhwar@wvumedicine.org

304-598-4151

Study Officials

• Vinay Badhwar, MD

  West Virginia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Executive Chair, Heart & Vascular Institute

Model Details: 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.

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: December 14, 2021
• Study Start: March 16, 2022
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: May 5, 2026
• Results First Posted: May 5, 2026

Record last verified: 2026-04

Locations

US (1)