The V-QUIN MDR TRIAL: A randomized controlled trial of six months of daily levofloxacin for the prevention of tuberculosis among household contacts of patients with multi-drug resistant tuberculosis
University of Sydney
2,006 participants
Mar 14, 2016
Interventional
Conditions
Summary
This is a randomized controlled trial of a six month course of an oral antibiotic treatment for latent tuberculosis infection (LTBI) in contacts of patients with MDR-TB. It will be conducted in 10 Provinces throughout Vietnam, in a study that will be integrated within the Vietnam National TB Program. The study will compare the incidence of TB, over 30 months follow-up, in participants randomised to six months of oral levofloxacin with the incidence of those randomised to placebo.
Eligibility
Inclusion Criteria12
- Eligibility for screening, prior to randomization, include:
- Any age
- Living in the same household** as the index patient within the previous 3 months
- Eligibility for randomization include:
- Living in the same household as the index patient within the previous 3 months
- Any age
- One of:
- (a) Tuberculin skin test positive (a size of 10mm or greater at first reading); OR
- (b) Any TST size if known to be HIV positive or severely malnourished; OR
- (c) New TST conversion on the second reading
- Note that in the initial period of the study, we enrolled contacts <15 years and conducted periodic screening for disease. However, they were not randomised to receive the intervention. From February 16th 2019, contacts of all ages were eligible randomisation to receive the intervention, following approval by the relevant institutional review boards / ethics committees.
- A household contact is defined as: “A person who shares (or has shared) the same enclosed living space for one or more nights each week, or for frequent or extended time periods during the day with the index case, during the 3 months before the commencement of the current treatment episode.
Exclusion Criteria34
- Eligibility for participants 15 years and over:
- A diagnosis of current active TB disease made during initial assessment¶
- Known to be pregnant*
- Unable to take oral medication
- Body weight < 3kg
- Unwilling or unable to participate in follow-up for 30 months
- Currently breast feeding**
- Known allergy to fluoroquinolone antibiotics, or history of severe tendinopathy related to fluoroquinolones
- Currently taking another medication reported to increase the cardiac QTc interval (e.g. amiodarone, sotalol, disopyramide, quinidine, procainamide, terfenadine).
- Documented previous treatment for MDR-TB
- Documented treatment with antibiotics that are active against MDR-TB in the previous month (including fluoroquinolones).
- Prior severe blistering reaction to tuberculin
- End stage liver failure (class Child-Pugh C).
- Dialysis-dependent chronic kidney disease
- A baseline liver function test (AST, ALT or ALP) more than 3 times the upper limit of normal
- Baseline ECG shows the QT segment (corrected for the R-R interval) is >450ms
- Kidney tests show end stage kidney disease (defined as an EGFR < 20mL/min)
- The platelet count is < 50x109 cells/L
- For children aged <15 years:
- Body weight < 3kg
- Current active TB disease
- Unable to take oral medication
- Unwilling or unable to participate in follow-up for 30 months
- Known allergy to fluoroquinolone antibiotics, or history of severe tendinopathy related to fluoroquinolones
- Currently taking another medication reported to increase the cardiac QTc interval (e.g. amiodarone, sotalol, disopyramide, quinidine, procainamide, terfenadine).
- Documented previous treatment for MDR-TB
- Documented treatment with antibiotics that are active against MDR-TB in the previous month (including fluoroquinolones).
- Prior severe blistering reaction to tuberculin
- End stage liver failure (class Child-Pugh C).
- Dialysis-dependent chronic kidney disease
- A baseline liver function test (AST or ALT) more than 3 times the upper limit of normal
- Kidney tests show end stage kidney disease (EGFR < 20mL/min)
- Platelet count < 50x109 cells/L
- Absence of informed parental consent
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Interventions
Six months of daily oral levofloxacin (dosing 3-5.9kg 62.5mg, 6-9.9kg 125mg; 10-15.9kg 250mg; 16-24.9kg 375mg; 25-49.99kg 500mg; 50kg and above 750mg). Compliance monitoring is based on pill count and self-report Screening for incident disease is performed for 30 months after enrollment, at 6, 12, 18, 24 and 30 months. Screening includes clinical assessment and chest radiography. Additional telephone-based symptom screening will be performed at 9, 15, 21 and 27 months, with clinical evaluation if symptoms are present (including new cough or sputum production for 2 weeks or more). No maximum duration of therapy. Patients will continue to receive treatment beyond 180 days, if they have not completed the requisite number of doses by that time.
Locations(1)
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ACTRN12616000215426