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)

NCT04211649 | Not Yet Recruiting Phase 4 DMC

• 2 other identifiers: 19_RIPH1_072024-516533-13-00
• Study Type: interventional
• Target: 220
• Locations: 4 countries
• Sites: 4

Brief 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.

Conditions

Mild Leptospirosis

Keywords

neglected infectious; tropical diseases; emerging diseases; mild leptospirosis; insular context; antibiotics; short treatment period; non-inferiority trial

Outcome Measures

Primary Outcomes (3)

• Treatment failure

  \- occurrence of a complication: * 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 * hematologic failure with hemoglobin \<7 g / L requiring red blood cell transfusion or platelets \< 20 G / L requiring platelet transfusion * Ventilatory failure defined by PaO2 / Fi O2 ratio \<300 mmHg or resort to mechanical ventilation * Renal failure defined by serum creatinine \> 301 μmol / L or resort to renal dialysis * Hepatic failure defined by total bilirubinemia\> 101 μmol / L * Heart failure (eg: ECG anomalies, myocarditis, cardiogenic shock) * Neurologic affection such as meningitis, encephalitis, intracerebral hemorragia, stroke * Ocular symptoms such as uveitis. * Hemoptysis, lesional pulmonary oedema for pulmonary affection * Hemorrhagic syndrome , or

  7 days from the beginning of antibiotic therapy

• Treatment failure

  continued fever (body temperature \>38°C) 5 days after the start of antibiotic therapy, or fever reappearance (body temperature \>38°C) observed 24 hours after initial apyrexia (body temperature \<38°C). Both cases exclude fever due to a cause not attributable to leptospirosis infection. Or,

  7 days from the beginning of antibiotic therapy

• Treatment failure

  death

  7 days from the beginning of antibiotic therapy

Secondary Outcomes (15)

• Evolution of clinical characteristics according to 3-day versus 7-day treatment duration

  21 days

• Evolution functional signs according to 3-day versus 7-day treatment duration

  21 days

• No evolution of infection at 21 days from start of antibiotic therapy according to 3-day versus 7-day treatment duration

  21 days

• Evolution of Quality of life according to 3-day versus 7-day treatment duration

  21 days

• Evolution of bilirubinemia values according to 3-day versus 7-day treatment duration

  21 days

Study Arms (2)

3 days of antibiotherapy

EXPERIMENTAL

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

Drug: 3 days of antibiotherapy

7 days of antibiotherapy (Amoxycilline or Doxycycline)

NO INTERVENTION

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

Interventions

3 days of antibiotherapy DRUG

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

3 days of antibiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient consulting at a recruiting hospital center
• Clinical and biological suspicion of leptospirosis, confirmed by serological rapid testing or PCR at most 72 hours after start of antibiotic treatment
• 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
• Acceptance of participation in the clinical trial and in the follow-up process at 7 and 21 days (from start of antibiotic therapy)
• Provision of a signed consent form from the study participant

You may not qualify if:

• 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)
• Hematologic failure with hemoglobin \<7 g / dL requiring red blood cell transfusion (74) or platelets \<20 G / L requiring platelet transfusion (75)
• Ventilatory failure defined by PaO2 / Fi O2 ratio \<300 mmHg (76) or resort to mechanical ventilation
• Renal failure defined by serum creatinine \> 301 μmol / L 76) or resort to renal dialysis
• Hepatic failure defined by total bilirubinemia\> 101 μmol / L (76)
• Heart failure (eg: ECG anomalies, myocarditis, cardiogenic shock)
• Neurologic affection such as meningitis, encephalitis, intracerebral hemorragia, stroke
• Ocular symptoms such as uveitis.
• Hemoptysis, lesional pulmonary oedema for pulmonary affection
• Hemorrhagic syndrome
• 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

Sponsors & Collaborators

• University Hospital Center of Martinique: lead
• University Hospital of Guadeloupe: collaborator
• Centre Hospitalier de Cayenne: collaborator
• Centre Hospitalier Universitaire de la Réunion: collaborator
• Hôpital de Mayotte: collaborator

Study Sites (5)

Centre Hospitalier Andrée Rosemond (CH de Cayenne)

Cayenne, 97300, French Guiana

Location

University Hospital of Guadeloupe

Pointe-à-Pitre, 97159, Guadeloupe

Location

Centre Hospitalier Universitaire de Martinique

Fort-de-France, 97200, Martinique

Location

Centre Hospitalier de Mayotte

Mamoudzou, 97600, Mayotte

Location

Centre Hospitalier Universitaire Sud Réunion

Saint-Pierre, 97448, Reunion

Location

Study Officials

• André CABIE, Professor

  University Hospital of Martinique

  STUDY DIRECTOR

Central Study Contacts

Janick JEAN-MARIE, Master

CONTACT

0596 59 26 97; janick.jean-marie@chu-martinique.fr

Isabelle CALMONT, Master

CONTACT

0596 59 26 97; isabelle.calmont@chu-martinique.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 26, 2019
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: July 18, 2024

Record last verified: 2024-07

Locations

MA (1); FR (1); RE (1); GU (1)