A Phase 4 interventional study of 3 days of antibiotherapy in Mild Leptospirosis, sponsored by University Hospital Center of Martinique. Not yet recruiting at 5 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-07-18.
Sponsored by University Hospital Center of Martinique · Phase 4, Interventional, and Treatment
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 :
25 studies on the registry are indexed under Leptospirosis; 11 are open to participants now.
This study's planned enrollment of 220 is below the median of 260 across 14 interventional studies indexed under Leptospirosis.
Browse Leptospirosis studies →University Hospital Center of Martinique is the lead sponsor of 79 studies on the registry; 21 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Presence of one of the severity criteria appearing between the time of first patient care at the hospital and study inclusion:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The patient viewed for the first time at the hospital and suspected of leptospirosis received a probabilistic antibiotherapy
Drug: 3 days of antibiotherapy
When the leptospirosis is confirmed ( PCR Leptospirosis positive) the pobabilistic antibiotherapy is switched to a prophylactic antibiotherapy with Amoxicillin or Doxycycline.
Reduce at 3 days of antibiotherapy for the treatment of mild leptospirosis
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
Time frame: 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,
Time frame: 7 days from the beginning of antibiotic therapy
Treatment failure
death
Time frame: 7 days from the beginning of antibiotic therapy
Evolution of clinical characteristics according to 3-day versus 7-day treatment duration
measure of body temperature * assessment of functional signs * no evolution of infection at 21 days from start of antibiotic therapy) * Absence of clinical symptoms (jaundice, nausea, abdominal pain, myalgia, and arthlagia) * Normalization of biological parameters (creatinine, bilirubin, platelets, hemoglobin) * Quality of life criteria evaluated by the EQ5D questionnaire
Time frame: 21 days
Evolution functional signs according to 3-day versus 7-day treatment duration
Assessment of functional signs
Time frame: 21 days
No evolution of infection at 21 days from start of antibiotic therapy according to 3-day versus 7-day treatment duration
Absence of clinical symptoms such as jaundice, nausea, abdominal pain, myalgia, and arthlagia Normalization of biological parameters (creatinine, bilirubin, platelets, hemoglobin)
Time frame: 21 days
Evolution of Quality of life according to 3-day versus 7-day treatment duration
Quality of life criteria evaluated by the EQ5D questionnaire (scale from 0 to 100 with 0 means worst imaginable health state; 100 means best imaginable health state
Time frame: 21 days
Evolution of bilirubinemia values according to 3-day versus 7-day treatment duration
μmol / L
Time frame: 21 days
Evolution of serum creatinine values according to 3-day versus 7-day treatment duration
μmol / L
Time frame: 21 days
Evolution of hemoglobin values according to 3-day versus 7-day treatment duration
G / L
Time frame: 21 days
Length of hospital stay according to 3-day versus 7-day treatment duration
Time frame: 21 days
Factors associated with treatment failure : Serogroup of leptospira
Time frame: 7 days
Factors associated with treatment failure : Genovar of leptospira
Time frame: 7 days
Factors associated with treatment failure : quantitative leptospiremia (blood) before antibiotic treatment
quantitative leptospiremia (blood) at start of antibiotic therapy
Time frame: 7 days
Factors associated with treatment failure : quantitative leptospiremia (blood) Day+3 of antibiotic treatment
quantitative leptospiremia (blood) at 3 days from start of antibiotic therapy
Time frame: 3 days
Factors associated with treatment failure : Delay between symptom onset and beginning of treatment
day (unit)
Time frame: From day of frist symptoms until enrollment (with a maximum of 7 days between first symptom and date of enrollement)
Factors associated with treatment failure : Presence of co-morbidities
day (unit)
Time frame: From the enrollment, until followup visit 1 (Day 0+7days)
Tolerance to treatment
Tolerance to treatment assessed by the occurrence of Jarisch-Herxheimer reactions, as well as adverse event reporting based on a standardized and internationally recognized toxicity table for adults
Time frame: 21 days
This study is not yet recruiting, as verified in Jul 2024. You cannot join it, but the record below documents what was studied.
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University Hospital Center of Martinique