Partial Oral Antimicrobials to Treat Infective Endocarditis in People Who Inject Drugs

NCT04544306 | Recruiting

• 1 other identifier: 10418
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Infective endocarditis (IE) is a serious infection associated with significant morbidity and mortality. Recent studies demonstrated an increased risk of infective endocarditis in people who inject drugs (PWIDs). PWIDs have a high rate of non-compliance with hospital admissions and leaving against medical advice. A recent landmark randomized controlled trial demonstrated similar outcomes when comparing partial oral antimicrobial therapy to continued intravenous antimicrobial therapy in the general population. Performing a trial to explore the non-inferiority of oral compared to intravenous antimicrobial therapy in PWIDs is essential in advancing patient care in this high risk increasing population.

Conditions

Infective Endocarditis

Keywords

PWID; oral antibiotics; endocarditis

Outcome Measures

Primary Outcomes (2)

• The number of eligible participants who are approached for consent to participate will be recorded.

  Number of individuals who are eligible to be enrolled during the study time frame.

  18 months

• The percentage who consent for enrollment will be determined as well as the reasons for refusal.

  Number of patients that participate as well as those who refuse to enroll during the study time frame.

  18 months

Secondary Outcomes (2)

• Percentage of enrolled patients for whom 90 day survival data is able to be confirmed.

  3 months after randomization

• Percentage of enrolled patients who continue in their assigned treatment arm (Oral or Parenteral) throughout the treatment interval.

  6 weeks post enrollment

Study Arms (2)

Control arm

NO INTERVENTION

Standard of Care (intravenous antimicrobial therapy according to the American Heart Association Guideline 2015)

Partial oral treatment arm

EXPERIMENTAL

The mode of antimicrobial delivery is switched to oral therapy after at least 10 days of IV therapy, guided by antimicrobial susceptibility

Other: Partial oral antimicrobial therapy

Interventions

Partial oral antimicrobial therapy OTHER

Switch intravenous antimicrobial therapy to oral after an initial period of 10 days to oral antimicrobial therapy. Antimicrobial choices will be guided by antimicrobial susceptibilities.

Partial oral treatment arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥ 18 years with self-reported intravenous drug use within 3 months of admission
• Transthoracic and/or transesophageal echocardiogram for IE diagnosis should be done within 48 hours of randomization
• Patients meet the modified Duke criteria for possible or definite infective endocarditis diagnosis
• Polymicrobial infections may be enrolled if an acceptable oral regimen can be constructed containing at least 2 agents against each gram-positive organism and one against each gram-negative
• Fungal Endocarditis may be enrolled if susceptibility to an oral azole is confirmed
• IE Patients who demonstrate improvement with initial intravenous therapy will be recruited
• Patients should receive a minimum of 10 days initial IV therapy and should have a minimum of 14 days remaining of their antimicrobial therapy

You may not qualify if:

• Undrained valvular, perivalvular, or cardiac abscess on echocardiogram studies
• Failure to show improvement to initial intravenous antimicrobial therapy
• Oral antibiotic malabsorption due to gastrointestinal disorders
• Acutely intoxicated patients who are not able to provide informed consent

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (2)

University Hospital

London, Ontario, Canada

RECRUITING

Victoria Hospital

London, Ontario, Canada

RECRUITING

Related Publications (18)

• Tookes H, Diaz C, Li H, Khalid R, Doblecki-Lewis S. A Cost Analysis of Hospitalizations for Infections Related to Injection Drug Use at a County Safety-Net Hospital in Miami, Florida. PLoS One. 2015 Jun 15;10(6):e0129360. doi: 10.1371/journal.pone.0129360. eCollection 2015.

  PMID: 26075888 BACKGROUND

• Weir MA, Slater J, Jandoc R, Koivu S, Garg AX, Silverman M. The risk of infective endocarditis among people who inject drugs: a retrospective, population-based time series analysis. CMAJ. 2019 Jan 28;191(4):E93-E99. doi: 10.1503/cmaj.180694.

  PMID: 30692105 BACKGROUND

• 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

• Kasper KJ, Manoharan I, Hallam B, Coleman CE, Koivu SL, Weir MA, McCormick JK, Silverman MS. A controlled-release oral opioid supports S. aureus survival in injection drug preparation equipment and may increase bacteremia and endocarditis risk. PLoS One. 2019 Aug 9;14(8):e0219777. doi: 10.1371/journal.pone.0219777. eCollection 2019.

  PMID: 31398210 BACKGROUND

• Rodger L, Glockler-Lauf SD, Shojaei E, Sherazi A, Hallam B, Koivu S, Gupta K, Hosseini-Moghaddam SM, Silverman M. Clinical Characteristics and Factors Associated With Mortality in First-Episode Infective Endocarditis Among Persons Who Inject Drugs. JAMA Netw Open. 2018 Nov 2;1(7):e185220. doi: 10.1001/jamanetworkopen.2018.5220.

  PMID: 30646383 BACKGROUND

• Rodger L, Shah M, Shojaei E, Hosseini S, Koivu S, Silverman M. Recurrent Endocarditis in Persons Who Inject Drugs. Open Forum Infect Dis. 2019 Sep 9;6(10):ofz396. doi: 10.1093/ofid/ofz396. eCollection 2019 Oct.

  PMID: 31660358 BACKGROUND

• Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Tleyjeh IM, Rybak MJ, Barsic B, Lockhart PB, Gewitz MH, Levison ME, Bolger AF, Steckelberg JM, Baltimore RS, Fink AM, O'Gara P, Taubert KA; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation. 2015 Oct 13;132(15):1435-86. doi: 10.1161/CIR.0000000000000296. Epub 2015 Sep 15.

  PMID: 26373316 BACKGROUND

• Heldman AW, Hartert TV, Ray SC, Daoud EG, Kowalski TE, Pompili VJ, Sisson SD, Tidmore WC, vom Eigen KA, Goodman SN, Lietman PS, Petty BG, Flexner C. Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Am J Med. 1996 Jul;101(1):68-76. doi: 10.1016/s0002-9343(96)00070-8.

  PMID: 8686718 BACKGROUND

• Al-Omari A, Cameron DW, Lee C, Corrales-Medina VF. Oral antibiotic therapy for the treatment of infective endocarditis: a systematic review. BMC Infect Dis. 2014 Mar 13;14:140. doi: 10.1186/1471-2334-14-140.

  PMID: 24624933 BACKGROUND

• Tissot-Dupont H, Gouriet F, Oliver L, Jamme M, Casalta JP, Jimeno MT, Arregle F, Lavoute C, Hubert S, Philip M, Martel H, Riberi A, Habib G, Raoult D. High-dose trimethoprim-sulfamethoxazole and clindamycin for Staphylococcus aureus endocarditis. Int J Antimicrob Agents. 2019 Aug;54(2):143-148. doi: 10.1016/j.ijantimicag.2019.06.006. Epub 2019 Jun 8.

  PMID: 31181351 BACKGROUND

• Suzuki J, Johnson J, Montgomery M, Hayden M, Price C. Outpatient Parenteral Antimicrobial Therapy Among People Who Inject Drugs: A Review of the Literature. Open Forum Infect Dis. 2018 Aug 7;5(9):ofy194. doi: 10.1093/ofid/ofy194. eCollection 2018 Sep.

  PMID: 30211247 BACKGROUND

• Eaton EF, Mathews RE, Lane PS, Paddock CS, Rodriguez JM, Taylor BB, Saag MS, Kilgore ML, Lee RA. A 9-Point Risk Assessment for Patients Who Inject Drugs and Require Intravenous Antibiotics: Focusing Inpatient Resources on Patients at Greatest Risk of Ongoing Drug Use. Clin Infect Dis. 2019 Mar 5;68(6):1041-1043. doi: 10.1093/cid/ciy722.

  PMID: 30165395 BACKGROUND

• Beieler AM, Dellit TH, Chan JD, Dhanireddy S, Enzian LK, Stone TJ, Dwyer-O'Connor E, Lynch JB. Successful implementation of outpatient parenteral antimicrobial therapy at a medical respite facility for homeless patients. J Hosp Med. 2016 Aug;11(8):531-5. doi: 10.1002/jhm.2597. Epub 2016 Apr 27.

  PMID: 27120700 BACKGROUND

• Norris AH, Shrestha NK, Allison GM, Keller SC, Bhavan KP, Zurlo JJ, Hersh AL, Gorski LA, Bosso JA, Rathore MH, Arrieta A, Petrak RM, Shah A, Brown RB, Knight SL, Umscheid CA. 2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy. Clin Infect Dis. 2019 Jan 1;68(1):e1-e35. doi: 10.1093/cid/ciy745.

  PMID: 30423035 BACKGROUND

• Silverman M, Slater J, Jandoc R, Koivu S, Garg AX, Weir MA. Hydromorphone and the risk of infective endocarditis among people who inject drugs: a population-based, retrospective cohort study. Lancet Infect Dis. 2020 Apr;20(4):487-497. doi: 10.1016/S1473-3099(19)30705-4. Epub 2020 Jan 22.

  PMID: 31981474 BACKGROUND

• Dagher M, Fowler VG Jr, Wright PW, Staub MB. A Narrative Review of Early Oral Stepdown Therapy for the Treatment of Uncomplicated Staphylococcus aureus Bacteremia: Yay or Nay? Open Forum Infect Dis. 2020 May 5;7(6):ofaa151. doi: 10.1093/ofid/ofaa151. eCollection 2020 Jun.

  PMID: 32523971 BACKGROUND

• Tan C, Shojaei E, Wiener J, Shah M, Koivu S, Silverman M. Risk of New Bloodstream Infections and Mortality Among People Who Inject Drugs With Infective Endocarditis. JAMA Netw Open. 2020 Aug 3;3(8):e2012974. doi: 10.1001/jamanetworkopen.2020.12974.

  PMID: 32785635 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

MeSH Terms

Conditions

Endocarditis

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Michael Silverman, MD,FRCP

  LHSC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Silverman, MD,FRCP

CONTACT

5196466100; michael.silverman@sjhc.london.on.ca

Sarah Shalhoub, MD

CONTACT

5196466100

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair/Chief,Infectious Diseases Division

Study Record Dates

• First Submitted: August 25, 2020
• First Posted: September 10, 2020
• Study Start: June 1, 2021
• Primary Completion: December 30, 2024
• Study Completion: June 30, 2025
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)