Multicenter, Randomized, Open-label Non-inferiority Trial, 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)
Multicenter, Randomized, Open-label Non-inferiority Trial, 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)
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.
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.
Main objective :
Compare the efficacy of a 3-day antibiotic therapy period with the standard period of 7 days in mild leptospirosis patients seen at the hospital in 5 French overseas departments (Martinique, Guadeloupe, French Guiana, Reunion, Mayotte)
Secondary objectives :
Inclusion Criteria:
Exclusion Criteria:
Presence of one of the severity criteria appearing between the time of first patient care at the hospital and study inclusion:
Diagnosis of another bacterial infection documented during initial patient assessment (e.g. Gram-negative bacteremia, digestive tract infection, bacterial pneumonia)
Intake of antibiotics, active on leptospirosis, the week before clinical and biological suspicion of leptospirosis
Leptospirosis diagnosis by PCR or serological rapid testing after the 7th day from symptom onset
Pregnant or lactating woman, or woman of childbearing age without effective contraception
Previous hypersensitivity to β-lactams and doxycycline or contraindication to the latter's use
Ongoing treatment that is contraindicated with one of the study treatments
janick.jean-marie@chu-martinique.fr0596 59 26 97 ext. +596
isabelle.calmont@chu-martinique.fr0596 59 26 97 ext. +596
Cayenne, 97300, French Guiana
fanny.abad@ch-cayenne.fr0594 39 77 99 ext. +594
elvire.couchy@chu-gaudeloupe.fr0590 91 19 30 ext. +590
janick.jean-marie@chu-martinique.fr0596 59 26 97 ext. +596
veronique.pelonde-erimee@chu-martinique.fr0596 59 26 97 ext. +596
m.niang@chmayotte.fr02 69 61 80 00 ext. +262
antoine.bertolotti@chu-reunion.fr02 62 35 90 00 ext. +262