An interventional study of Partial oral antimicrobial therapy in Infective Endocarditis, sponsored by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's. Recruiting at 2 sites in Canada. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-02-26.
Sponsored by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's · Not applicable, Interventional, and Treatment
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.
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.
Exclusion Criteria:
Standard of Care (intravenous antimicrobial therapy according to the American Heart Association Guideline 2015)
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.
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.
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.
Time frame: 18 months
Percentage of enrolled patients for whom 90 day survival data is able to be confirmed.
Number of patients with all cause death or survival documented at 90 days post enrollment.
Time frame: 3 months after randomization
Percentage of enrolled patients who continue in their assigned treatment arm (Oral or Parenteral) throughout the treatment interval.
The assessment of compliance with oral or parenteral antibiotics will be carried out during treatment.
Time frame: 6 weeks post enrollment
Plan to share: No
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's