Ciprofloxacin for the Prevention of Meningococcal Meningitis

Study Overview
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Brief Summary
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This study evaluates the effect of antibiotic prophylaxis with ciprofloxacin, given to the contacts of meningitis cases, on the overall attack rate of meningitis during an epidemic. One third of enrolled villages will receive standard care; in one-third of villages, household contacts of meningitis cases will be offered a single dose of oral ciprofloxacin; and in one-third of villages, the entire village will be offered a single dose of oral ciprofloxacin after the notification of the first case in the village.

Detailed Description
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Antibiotic prophylaxis is not currently recommended for contacts of cases during a meningitis epidemic in the African Meningitis Belt. Reactive vaccination campaigns are the preferred strategy for prevention during an epidemic. A novel strain of meningococcus, Neisseria meningitidis serogroup C (NmC), began circulating in Nigeria in 2013 and caused a major epidemic with over 10 000 cases in Nigeria and Niger in 2015. There is currently a global shortage of vaccine against NmC, and a recent WHO expert panel called for the formal evaluation of antibiotic prophylaxis as another epidemic response strategy. When taken as a single dose, oral ciprofloxacin effectively eliminates nasopharyngeal carriage of meningococcus. This trial aims to investigate two different antibiotic prophylaxis strategies during an epidemic of meningococcal meningitis: ciprofloxacin prophylaxis to household members of cases and village-wide prophylaxis after the notification of a case in a village. These two strategies will be compared to villages receiving standard care.

Official Title
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Cluster-randomized Trial to Evaluate the Impact of Ciprofloxacin for Contacts of Cases of Meningococcal Meningitis as an Epidemic Response

Conditions
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Meningitis, Meningococcal

Intervention / Treatment
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* Drug: Ciprofloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Resident in a village included in the study area Exclusion Criteria: Patients currently exhibiting symptoms of meningitis (to be immediately referred for further care) Persons with a known allergy to fluoroquinolone antibiotics.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard care<br>No chemoprevention for contacts of cases of meningitis (current standard of care) with a health promotion visit by a study nurse after the first notification of cases during the epidemic | |
| Active Comparator: Household prophylaxis<br>Chemoprophylaxis with a single dose of oral ciprofloxacin for household members of reported cases of meningitis. For participants age >12 years: 500 mg tablet; age 5-12 years: 250 mg tablet; age 1-4 years: 125 mg tablet; age 3-11 months: 100 mg (2 ml oral suspension); age <3 months: 75 mg (1.5 ml oral suspension). | Drug: Ciprofloxacin<br>* Single-dose oral ciprofloxacin<br>* Other names: Cipro;|
| Active Comparator: Village prophylaxis<br>Chemoprophylaxis with ciprofloxacin in the setting of a village-wide distribution after the notification of the first case of meningitis in a village. For participants age >12 years: 500 mg tablet; age 5-12 years: 250 mg tablet; age 1-4 years: 125 mg tablet; age 3-11 months: 100 mg (2 ml oral suspension); age <3 months: 75 mg (1.5 ml oral suspension). | Drug: Ciprofloxacin<br>* Single-dose oral ciprofloxacin<br>* Other names: Cipro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Meningitis Attack Rate | The primary outcome aims to evaluate the impact of a chemoprevention strategy as a public health intervention during a meningitis outbreak, which is best evaluated by looking at the overall attack rates in the study area. | From enrollment of a village through study completion, an average of 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with ciprofloxacin-resistant enterobacteriaceae in their stools | A substudy is proposed to compare rates of acquisition of ciprofloxacin resistance among participants in the standard care arm and participants in the village prophylaxis arm. 20 participants in 10 villages in each of the two arms will be asked to provide stool samples on days 0, 7 and 28 | Prior to ciprofloxacin dosing (day 0) and at 7 days and 28 days post-ciprofloxacin dosing | 
| Proportion of patients who received ciprofloxacin who develop meningitis |  | From enrollment of a village through study completion, an average of 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neisseria meningitidis, Ciprofloxacin, Chemoprevention