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)

NCT ID: NCT04211649

Last Updated: 2024-07-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-01

Study Completion Date

2028-02-01

Brief Summary

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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.

Detailed Description

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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

Conditions

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Mild Leptospirosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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3 days of antibiotherapy

The patient viewed for the first time at the hospital and suspected of leptospirosis received a probabilistic antibiotherapy

Group Type EXPERIMENTAL

3 days of antibiotherapy

Intervention Type DRUG

Reduce at 3 days of antibiotherapy for the treatment of mild leptospirosis

7 days of antibiotherapy (Amoxycilline or Doxycycline)

When the leptospirosis is confirmed ( PCR Leptospirosis positive) the pobabilistic antibiotherapy is switched to a prophylactic antibiotherapy with Amoxicillin or Doxycycline.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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3 days of antibiotherapy

Reduce at 3 days of antibiotherapy for the treatment of mild leptospirosis

Intervention Type DRUG

Eligibility Criteria

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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 rapid testing or PCR at most 72 hours after start of antibiotic treatment
4. Affiliated or beneficiary of a social security scheme (For French Guiana, patients benefiting from State Medical Aid (AME) will be considered, in accordance with the provisions 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 7 and 21 days (from start of antibiotic therapy)
6. Provision of a signed consent form from the study participant

Exclusion Criteria

1. Presence of one of the 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 (73)
2. Hematologic failure with hemoglobin \<7 g / dL requiring red blood cell transfusion (74) or platelets \<20 G / L requiring platelet transfusion (75)
3. Ventilatory failure defined by PaO2 / Fi O2 ratio \<300 mmHg (76) or resort to mechanical ventilation
4. Renal failure defined by serum creatinine \> 301 μmol / L 76) or resort to renal dialysis
5. Hepatic failure defined by total bilirubinemia\> 101 μmol / L (76)
6. Heart failure (eg: ECG anomalies, myocarditis, cardiogenic shock)
7. Neurologic affection such as meningitis, encephalitis, intracerebral hemorragia, stroke
8. Ocular symptoms such as uveitis.
9. Hemoptysis, lesional pulmonary oedema for pulmonary affection
10. Hemorrhagic syndrome
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 or serological rapid testing after the 7th day from symptom onset
5. Pregnant or lactating woman, or woman of childbearing age without effective contraception
6. Previous hypersensitivity to β-lactams and doxycycline or contraindication to the latter's use
7. Ongoing treatment that is contraindicated with one of the study treatments
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital of Guadeloupe

UNKNOWN

Sponsor Role collaborator

Centre Hospitalier de Cayenne

OTHER

Sponsor Role collaborator

Centre Hospitalier Universitaire de la Réunion

OTHER

Sponsor Role collaborator

Hôpital de Mayotte

UNKNOWN

Sponsor Role collaborator

University Hospital Center of Martinique

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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André CABIE, Professor

Role: STUDY_DIRECTOR

University Hospital of Martinique

Locations

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Centre Hospitalier Andrée Rosemond (CH de Cayenne)

Cayenne, , French Guiana

Site Status

University Hospital of Guadeloupe

Pointe-à-Pitre, , Guadeloupe

Site Status

Centre Hospitalier Universitaire de Martinique

Fort-de-France, , Martinique

Site Status

Centre Hospitalier de Mayotte

Mamoudzou, , Mayotte

Site Status

Centre Hospitalier Universitaire Sud Réunion

Saint-Pierre, , Reunion

Site Status

Countries

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French Guiana Guadeloupe Martinique Mayotte Reunion

Central Contacts

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Janick JEAN-MARIE, Master

Role: CONTACT

0596 59 26 97 ext. +596

Isabelle CALMONT, Master

Role: CONTACT

0596 59 26 97 ext. +596

Facility Contacts

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William Faurous, MD

Role: primary

0594 39 77 99 ext. +594

Elvire Couchy, Master

Role: primary

0590 91 19 30 ext. +590

Janick Jean-Marie, Master

Role: primary

0596 59 26 97 ext. +596

Véronique PELONDE-ERIMME, Master

Role: backup

0596 59 26 97 ext. +596

Mohamadou NIANG, MD

Role: primary

02 69 61 80 00 ext. +262

Antoine BERTOLOTTI, MD

Role: primary

02 62 35 90 00 ext. +262

Other Identifiers

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2024-516533-13-00

Identifier Type: CTIS

Identifier Source: secondary_id

19_RIPH1_07

Identifier Type: -

Identifier Source: org_study_id

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