Comparing Two Antibiotic Therapy Periods (3 Versus 7 Days) in Patients With Mild Leptospirosis and Seen at the Hospital in 5 French Overseas Departments (Martinique, Guadeloupe, French Guiana, Reunion, Mayotte)

• Status: Not yet recruiting
• Trial end date: 2023-05-31
• Target enrollment: 0
• Participant gender: All

Summary

Leptospirosis is a globally distributed neglected tropical disease affecting subtropical and tropical areas, such as the Caribbean and the Indian Ocean, with favorable climatic conditions for disease transmission. It shows a strong seasonality, with epidemic potential especially after heavy rainfall. A recent systematic review by Costa et al. (2015) places leptospirosis among the leading zoonotic causes of morbidity and mortality worldwide, with 1.03 million cases and 58,900 deaths each year.

Leptospirosis is an important public health problem, particularly within economically vulnerable populations. It is also emerging as a health threat in new settings due to globalization and climate change. Disasters and extreme weather events are recognized to precipitate epidemics.

Clinical manifestations are highly polymorphic, ranging from an anicteric, influenza-like form to severe forms with hepato-renal or pulmonary failures which are associated with high mortality.

Antibiotic therapy should be prescribed early, as soon as leptospirosis is suspected and preferably within the first 5 days, before leptospira spread to the tissues. In the treatment of mild forms, usual antibiotics are oral amoxicillin or doxycycline for a standard treatment duration of 7 days. In hospitalized cases of leptospirosis, parenteral antibiotic therapy with ceftriaxone is often favored as first-line therapy.

The most widely used antibiotics in the French Caribbean and Indian Ocean regions are amoxicillin, doxycyclin and third generation cephalosporins such as ceftriaxone.

Research hypothesis:

The effects of shorter antibiotic therapy periods for other infectious diseases have been explored by several authors. The efficacy of short ceftriaxone treatment has been highlighted for typhoid fever or meningococcal meningitis. In a retrospective series of 21 cases, the interest of short treatment periods (3-6 days) for mild and severe leptospirosis has also been described. A minimal 3-day therapy period would seem necessary in order to biologically confirm leptospirosis diagnosis and to rule out other community-acquired infections.

Our study proposal is the conduct of a non-inferiority trial comparing a shortened antibiotic therapy period of 3 days with the standard treatment period of 7 days in patients with mild leptospirosis and seen at the hospital in 5 French overseas departments (Martinique, Guadeloupe, French Guiana, Reunion, Mayotte).

Originality and innovative aspects:

To our knowledge, the efficacy of a 3-day antibiotic therapy for mild leptospirosis, as compared to the standard 7 day period, has not yet been explored.

In addition, the LEPTO3 study will be among the first clinical trials to focus on the endemic public health problem, which is leptospirosis, at a large geographical level (Caribbean and Indian Ocean regions) and to involve a high level of collaboration between medical and scientific teams of these territories.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Center of Martinique
• Collaborators: Centre Hospitalier de Cayenne; Centre Hospitalier Universitaire de la Réunion; Hôpital de Mayotte; University Hospital of Guadeloupe
• Treatments: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antitubercular

Criteria

Inclusion Criteria:

1. Patient aged 18 years and above at the time of study inclusion

2. Patient consulting at a recruiting hospital center

3. Clinical and biological suspicion of leptospirosis, confirmed by PCR at most 72 hours after start of antibiotic treatment

4. Affiliate or beneficiary of a social security scheme.

5. Acceptance of participation in the clinical trial and in the follow-up process at 7 and 21 days (from start of antibiotic therapy), as well as signed consent form

Exclusion Criteria:

• 1. Presence of severity criteria appearing between the time of first patient care at the hospital and study inclusion:

1. Hemodynamic failure with onset of septic shock defined by persisting hypotension requiring vasopressor amines to maintain mean arterial pressure ≥65 mm Hg and blood lactates >2 mmol/L despite adequate volume resuscitation

2. Hematologic failure with hemoglobin <7 g / L requiring red blood cell transfusion or platelets <20 G / L requiring platelet transfusion

3. Ventilatory failure defined by PaO2 / Fi O2 ratio <300 mmHg or resort to mechanical ventilation

4. Renal failure defined by serum creatinine > 301 μmol / L or resort to renal dialysis

5. Hepatic failure defined by total bilirubinemia> 101 μmol / L 2. Diagnosis of another bacterial infection documented during initial patient assessment (e.g. Gram-negative bacteremia, digestive tract infection, bacterial pneumonia) 3. Intake of antibiotics, active on leptospirosis, the week before clinical and biological suspicion of leptospirosis 4. Leptospirosis diagnosis by PCR after the 7th day from symptom onset or after the 3rd day from beginning of treatment 5. Pregnant or lactating woman 6. Absence of contraception 7. Allergy or contraindication to amoxicillin and doxycycline