Oral Antibiotics for Infective Endocarditis

Recruiting at 1 trial location

Overseen By Sarah Shalhoub, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Must be taking: Oral antimicrobials

Disqualifiers: Cardiac abscess, Malabsorption, Intoxication, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the oral antibiotic treatment for infective endocarditis?

Research shows that oral antibiotic treatment for infective endocarditis is as effective as intravenous treatment in certain patients, especially those who are stabilized. This has been demonstrated in studies like the POET trial, which found that oral step-down therapy worked just as well as continuing with intravenous antibiotics. ^{1 2 3 4 5}

Is partial oral antibiotic therapy safe for treating infective endocarditis?

Research shows that partial oral antibiotic therapy for infective endocarditis is generally safe and has similar safety outcomes compared to intravenous therapy, as seen in studies comparing adverse events between the two methods. ^{1 2 3 5 6}

How is partial oral antibiotic therapy different from other treatments for infective endocarditis?

Partial oral antibiotic therapy for infective endocarditis is unique because it allows patients to switch from intravenous (IV) antibiotics to oral antibiotics after initial treatment, which can be more convenient and less invasive. This approach is particularly considered for select patients and is not yet well established, especially in those who inject drugs. ^{1 3 5 7 8}

Research Team

Michael Silverman, MD,FRCP

Principal Investigator

LHSC

Eligibility Criteria

This trial is for adults over 18 who inject drugs and have infective endocarditis, a serious heart infection. They must have used IV drugs recently, started IV antibiotics in the hospital for at least 10 days, and need at least two weeks more treatment. People with undrained abscesses around the heart or those not responding to initial treatment can't join.

Inclusion Criteria

My fungal heart infection responds to specific oral medication.

I have used intravenous drugs in the last 3 months.

I have an infection treatable with at least 2 drugs for gram-positive and 1 for gram-negative bacteria.

Exclusion Criteria

You have a heart infection that has not been treated.

My infection did not get better with initial IV antibiotics.

I am not currently intoxicated and can make informed decisions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either continued intravenous antimicrobial therapy or switch to oral antimicrobial therapy after at least 10 days of IV therapy

6 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a transthoracic echocardiogram within 72 hours of stopping therapy

3 months

1 visit at 3 months (in-person)

Treatment Details

Interventions

• Partial oral antimicrobial therapy

Trial Overview The study tests if taking antibiotics by mouth is as effective as continuing them through an IV in people who inject drugs and have heart infections. Participants will either continue their usual IV therapy or switch to oral pills after starting with IVs in the hospital.

Participant Groups

Group I: Partial oral treatment arm Experimental Treatment 1 Intervention

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

Group II: Control arm Active Control 1 Intervention

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

Partial oral antimicrobial therapy is already approved in European Union, United States for the following indications:

Approved in European Union as Partial Oral Antibiotic Therapy for:

• Infective endocarditis
• Bone and joint infections
• Uncomplicated bloodstream infections

Approved in United States as Partial Oral Antibiotic Therapy for:

• Infective endocarditis
• Bone and joint infections
• Uncomplicated bloodstream infections

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

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

Lead Sponsor

Trials

678

Recruited

421,000+

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

Lead Sponsor

Trials

668

Recruited

424,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Findings from Research

In a study of 11 patients with infectious endocarditis, including 9 who were injection drug users, partial oral antibiotic therapy showed no relapsed infections and all patients survived to hospital discharge and 90 days post-discharge.

The findings support the use of partial oral antibiotic treatment as a non-inferior alternative to intravenous therapy for endocarditis, even in high-risk populations like those who inject drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Partial oral antibiotic treatment of endocarditis in patients who inject drugs: a case series. Miller, K., Evans, E., Sheridan, KR., et al.[2022]

In the clinical implementation of the POET regimen for treating infective endocarditis, 43% of eligible patients were successfully transitioned to oral step-down antibiotic therapy, demonstrating the feasibility of this approach.

Patients receiving oral therapy had a lower incidence of all-cause mortality (8% vs. 14% in the IV group) and a significantly shorter hospital stay (24 days vs. 43 days), suggesting that oral therapy may be a safe and effective alternative for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implementation of partial oral treatment in infective endocarditis: the Danish POETry study. Pries-Heje, MM., Hjulmand, JG., Lenz, IT., et al.[2023]

Oral antibiotic therapies for infective endocarditis (IE) show varying cure rates, with some regimens achieving between 77% and 100% success, particularly oral beta-lactams and ciprofloxacin combined with rifampin.

A small clinical trial suggests that oral ciprofloxacin with rifampin is as effective as intravenous antibiotics for treating uncomplicated right-sided S. aureus IE in intravenous drug users, but with significantly lower drug toxicity, making it a potential alternative when IV therapy is not feasible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral antibiotic therapy for the treatment of infective endocarditis: a systematic review. Al-Omari, A., Cameron, DW., Lee, C., et al.[2021]

In a study involving 236 patients from the POET trial, oral antibiotics like amoxicillin and linezolid showed high probabilities of target attainment (PTAs) ranging from 88% to 100%, indicating their effectiveness in treating infective endocarditis.

While some antibiotics like dicloxacillin had lower PTAs (9%-17%), the overall findings support the use of oral step-down therapy as a viable alternative to intravenous treatment, with most patients achieving effective drug levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy. Bock, M., Theut, AM., van Hasselt, JGC., et al.[2023]

In a study of 85 injection drug users with right-sided staphylococcal endocarditis, oral antibiotic treatment (ciprofloxacin and rifampin) was found to be effective, with only 5.2% treatment failures compared to 12.0% in the intravenous group, although this difference was not statistically significant.

Oral treatment was associated with significantly lower rates of drug toxicity (3%) compared to intravenous therapy (62%), highlighting the safety advantage of oral antibiotics in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Heldman, AW., Hartert, TV., Ray, SC., et al.[2019]

A systematic review of 10 studies found no significant difference in the overall rate of adverse events between oral and intravenous antimicrobial therapies, suggesting that both routes are similarly safe.

Injection site reactions were more common with intravenous therapy, but no serious drug-related adverse events were reported, indicating that both methods are generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of adverse events between oral and intravenous formulations of antimicrobial agents: a systematic review of the evidence from randomized trials. Kouranos, VD., Karageorgopoulos, DE., Peppas, G., et al.[2018]

The SWAB guidelines recommend specific antibiotic treatments for infective endocarditis based on factors like the type of infecting microorganism and whether the endocarditis is associated with a prosthetic valve, ensuring tailored and effective therapy.

For initial treatment, benzylpenicillin or flucloxacillin combined with gentamicin is advised for native valve infections, while vancomycin and gentamicin are recommended for prosthetic valve infections, highlighting the importance of prompt and appropriate antibiotic selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Optimalization of antibiotic policy in the Netherlands. VII. SWAB-guidelines for antimicrobial therapy in adults patients with infectious endocarditis]. Verhagen, DW., van der Feltz, M., Plokker, HW., et al.[2009]

Effective management of infective endocarditis requires a multidisciplinary approach within an 'Endocarditis team', emphasizing the importance of collaboration in patient care.

Initial treatment should involve parenteral antibiotics for at least 2 weeks, with a potential switch to oral antibiotics thereafter; however, aminoglycosides are no longer recommended for initial treatment of native valve Staphylococcus aureus endocarditis, and nearly 50% of patients may require valve surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of infectious endocarditis]. Hoen, B., Elfarra, M., Huttin, O., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Partial oral antibiotic treatment of endocarditis in patients who inject drugs: a case series. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Clinical implementation of partial oral treatment in infective endocarditis: the Danish POETry study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Oral antibiotic therapy for the treatment of infective endocarditis: a systematic review. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Comparison of adverse events between oral and intravenous formulations of antimicrobial agents: a systematic review of the evidence from randomized trials. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

[Optimalization of antibiotic policy in the Netherlands. VII. SWAB-guidelines for antimicrobial therapy in adults patients with infectious endocarditis]. [2009]

8. France pubmed.ncbi.nlm.nih.gov

[Treatment of infectious endocarditis]. [2019]