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)

Last updated: July 16, 2024
Sponsor: University Hospital Center of Martinique
Overall Status: Active - Not Recruiting

Phase

4

Condition

N/A

Treatment

3 days of antibiotherapy

Clinical Study ID

NCT04211649
19_RIPH1_07
2019-004037-17
2024-516533-13-00
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 serological rapidtesting or PCR at most 72 hours after start of antibiotic treatment

  4. Affiliated or beneficiary of a social security scheme (For French Guiana, patientsbenefiting from State Medical Aid (AME) will be considered, in accordance with theprovisions of article L1121-8-1 of the Public Health Code

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

  6. Provision of a signed consent form from the study participant

Exclusion

Exclusion Criteria:

  1. Presence of one of the severity criteria appearing between the time of first patientcare at the hospital and study inclusion:

  2. Hemodynamic failure with onset of septic shock defined by persistinghypotension requiring vasopressor amines to maintain mean arterial pressure ≥65mm Hg and blood lactates >2 mmol/L despite adequate volume resuscitation (73)

  3. Hematologic failure with hemoglobin <7 g / dL requiring red blood celltransfusion (74) or platelets <20 G / L requiring platelet transfusion (75)

  4. Ventilatory failure defined by PaO2 / Fi O2 ratio <300 mmHg (76) or resort tomechanical ventilation

  5. Renal failure defined by serum creatinine > 301 μmol / L 76) or resort to renaldialysis

  6. Hepatic failure defined by total bilirubinemia> 101 μmol / L (76)

  7. Heart failure (eg: ECG anomalies, myocarditis, cardiogenic shock)

  8. Neurologic affection such as meningitis, encephalitis, intracerebralhemorragia, stroke

  9. Ocular symptoms such as uveitis.

  10. Hemoptysis, lesional pulmonary oedema for pulmonary affection

  11. Hemorrhagic syndrome

  12. Diagnosis of another bacterial infection documented during initial patientassessment (e.g. Gram-negative bacteremia, digestive tract infection, bacterialpneumonia)

  13. Intake of antibiotics, active on leptospirosis, the week before clinical andbiological suspicion of leptospirosis

  14. Leptospirosis diagnosis by PCR or serological rapid testing after the 7th day fromsymptom onset

  15. Pregnant or lactating woman, or woman of childbearing age without effectivecontraception

  16. Previous hypersensitivity to β-lactams and doxycycline or contraindication to thelatter's use

  17. Ongoing treatment that is contraindicated with one of the study treatments

Study Design

Total Participants: 220
Treatment Group(s): 1
Primary Treatment: 3 days of antibiotherapy
Phase: 4
Study Start date:
October 01, 2024
Estimated Completion Date:
February 01, 2028

Study Description

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 :

  • Compare the evolution of clinical and biological characteristics in the 2 groups of patients (antibiotic therapy duration 3 days versus 7 days)

  • Compare lengths of hospital stay in the 2 groups of patients (antibiotic therapy duration 3 days versus 7 days)

  • Examine factors linked to a potential treatment failure in patients

  • Assess patient tolerance to treatment

Connect with a study center

  • Centre Hospitalier Andrée Rosemond (CH de Cayenne)

    Cayenne, 97300
    French Guiana

    Site Not Available

  • University Hospital of Guadeloupe

    Pointe-à-Pitre, 97159
    Guadeloupe

    Site Not Available

  • Centre Hospitalier Universitaire de Martinique

    Fort-de-France, 97200
    Martinique

    Site Not Available

  • Centre Hospitalier de Mayotte

    Mamoudzou, 97600
    Mayotte

    Site Not Available

  • Centre Hospitalier Universitaire Sud Réunion

    Saint-Pierre, 97448
    Réunion

    Site Not Available

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