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

February 23, 2024 updated by: Michael Silverman, MD, Lawson Health Research Institute

Partial Oral Antimicrobial Versus Intravenous Antimicrobial Therapy to Treat Infective Endocarditis in People Who Inject Drugs

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a randomized open-label study. Participants will be randomized 1:1 in blocks of 5 to either continued intravenous antimicrobial therapy or oral antimicrobial therapy after a minimum of 10 days of IV therapy. The antimicrobial choice will be based on antimicrobial susceptibility. All oral regimens for gram-positive organisms will include 2 different agents. Gram-negative pathogens will be treated with oral quinolones if susceptibility results are compatible. Decisions regarding ongoing inpatient or outpatient therapy will be made at the discretion of the attending physician. Outpatient follow up will be once weekly for 6 weeks and then at 3 months. At each follow-up visit, participants will undergo a general physical exam, and their adherence to therapy and general wellbeing will be assessed as well. Blood samples will be sent for a complete blood count, creatinine, C-reactive protein by the investigators to ensure continued improvement in response to therapy. Within 72 hours of stopping therapy, a transthoracic echocardiogram will be performed to determine response to therapy and to establish a new baseline to which subsequent echocardiograms if medically indicated would be compared to assess for relapse or development of a new IE. All lab tests are done at our affiliated hospitals. Investigators plan first on performing a feasibility study. In the feasibility study, investigators recruit a total of 50 patients and randomize 25 in each arm. Baseline characteristics, of clinical interest with a potential impact on prognosis, and patients' outcomes will be compared using the Chi-square test for categorical variables and the t-test and the Mann-Whitney test for continuous variables, when appropriate. To examine the association between oral antimicrobial therapy and 90-day mortality, investigators plan to perform a multivariable logistic regression analysis with oral therapy being the independent variable. The model will also include variables of clinical interest: diabetes, renal impairment, immune-compromising condition, age > 50, and evidence of embolization.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Sarah Shalhoub, MD
  • Phone Number: 5196466100

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada
        • Recruiting
        • University Hospital
        • Principal Investigator:
          • Michael Silverman, MD,FRCP
        • Principal Investigator:
          • Sarah Shalhoub, MD
        • Contact:
        • Contact:
      • London, Ontario, Canada

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adults ≥ 18 years with self-reported intravenous drug use within 3 months of admission
  2. Transthoracic and/or transesophageal echocardiogram for IE diagnosis should be done within 48 hours of randomization
  3. Patients meet the modified Duke criteria for possible or definite infective endocarditis diagnosis
  4. Infection with an organism susceptible to at least two oral antimicrobial agents from different classes. In gram-negative bacterial endocarditis, susceptibility to fluoroquinolones only would be acceptable for inclusion
  5. 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
  6. Fungal Endocarditis may be enrolled if susceptibility to an oral azole is confirmed
  7. IE Patients who demonstrate improvement with initial intravenous therapy will be recruited
  8. Patients should receive a minimum of 10 days initial IV therapy and should have a minimum of 14 days remaining of their antimicrobial therapy

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Control arm
Standard of Care (intravenous antimicrobial therapy according to the American Heart Association Guideline 2015)
Experimental: Partial oral treatment arm
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
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The number of eligible participants who are approached for consent to participate will be recorded.
Time Frame: 18 months
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.
Time Frame: 18 months
Number of patients that participate as well as those who refuse to enroll during the study time frame.
18 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of enrolled patients for whom 90 day survival data is able to be confirmed.
Time Frame: 3 months after randomization
Number of patients with all cause death or survival documented at 90 days post enrollment.
3 months after randomization
Percentage of enrolled patients who continue in their assigned treatment arm (Oral or Parenteral) throughout the treatment interval.
Time Frame: 6 weeks post enrollment
The assessment of compliance with oral or parenteral antibiotics will be carried out during treatment.
6 weeks post enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Lawson Health Research Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael Silverman, MD,FRCP, LHSC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 25, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 8, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 10, 2020

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 26, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 23, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 10418 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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