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

Sponsor

Lawson Health Research Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT04544306

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Infective Endocarditis	Other: Partial oral antimicrobial therapy	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2021

Anticipated Primary Completion Date :

Jun 30, 2022

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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.

Outcome Measures

Primary Outcome Measures

The number of eligible participants who are approached for consent to participate will be recorded. [18 months]
Number of individuals who are eligible to be enrolled during the study time frame.
The percentage who consent for enrollment will be determined as well as the reasons for refusal. [18 months]
Number of patients that participate as well as those who refuse to enroll during the study time frame.

Secondary Outcome Measures

Percentage of enrolled patients for whom 90 day survival data is able to be confirmed. [3 months after randomization]
Number of patients with all cause death or survival documented at 90 days post enrollment.
Percentage of enrolled patients who continue in their assigned treatment arm (Oral or Parenteral) throughout the treatment interval. [6 weeks post enrollment]
The assessment of compliance with oral or parenteral antibiotics will be carried out during treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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
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
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