Study of the Incidence of Jarisch-Herxheimer Reaction in Leptospirosis Patients in New Caledonia (LEPJARNC)

The objective of the study is to estimate the incidence of Jarisch-Herxheimer Reactions (JHR) during antibiotic treatment of human leptospirosis cases in New Caledonia.

Participants are patients managed in one of the 5 centres participating in the study, in whom a clinical doctor suspected leptospirosis. The average number of leptospirosis cases in New Caledonia is 89 per year. Given the proportion of positive diagnostic tests (approximately 10%) 900 inclusions are planned for this study.

Patients are included at the time of the consultation during which leptospirosis is suspected, before the initiation of their antibiotic therapy and independently of the clinical form they presented.

Data (socio-demographic and health) and blood samples will be collected at 3 points in the study: at baseline, three hours and six hours after antibiotic treatment.

This study will allow better management of patients with leptospirosis.

Study Overview

• Status: Recruiting
• Conditions: Leptospirosis; Jarisch Herxheimer Reaction
• Intervention / Treatment: Other: Blood collection; Other: Data collection

Detailed Description

The objective of the study is to estimate the incidence of Jarisch-Herxheimer Reactions (JHR) during antibiotic treatment of human leptospirosis cases in New Caledonia.

Secondary objectives of the study are to describe the JHR during leptospirosis (describe clinical, haemodynamic and cytokine response parameters), to describe the effects of the progressive introduction of antibiotic (ATB) for the treatment of leptospirosis and to harmonise management practices for patients with leptospirosis in NC.

Participants are patients managed in one of the 5 centres participating in the study, in whom a clinical doctor suspected leptospirosis. The average number of leptospirosis cases in New Caledonia (NC) is 89 per year. Given the proportion of positive diagnostic tests (approximately 10%) 900 inclusions are planned for this study.

Patients are included at the time of the consultation during which leptospirosis is suspected, before the initiation of their antibiotic therapy and independently of the clinical form they presented.

Blood samples will be collected at 3 points in the study: at baseline, three hours and six hours after antibiotic treatment.

Data will be collected at 4 points in the study: at baseline, three hours, six hours after antibiotic treatment and one day after treatment introduction (last point by phone call).

The data obtained will allow us to describe for the first time, in a prospective study, the JHR associated with leptospirosis in a significant number of patients.

The data obtained will also help to describe the impact of a therapeutic strategy on the evolution of the disease, which has not yet been evaluated. This study also aims to help harmonise the management of patients with leptospirosis in NC.

This study will allow better management of patients with leptospirosis.

• Study Type: Interventional
• Enrollment (Anticipated): 900
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julie CAGLIERO, PhD; Phone Number: +687 93 71 37; Email: jcagliero@pasteur.nc

Study Locations

• New Caledonia
  • Koné, New Caledonia
    • Not yet recruiting
    • Centre Hospitalier du Nord
    • Contact: Olivier Kesteman, Dr
  • Koumac, New Caledonia
    • Recruiting
    • Centre Hospitalier du Nord
    • Contact: Patrick Lefevre, Dr
  • Poindimié, New Caledonia
    • Not yet recruiting
    • Centre Hospitalier du Nord
    • Contact: Francois Baur, Dr
  • Nouvelle Calédonie
    • Bourail, Nouvelle Calédonie, New Caledonia
      • Not yet recruiting
      • Centre Médico-Social Jeanne Boutin
      • Contact: Leo Vincent, Dr
    • Nouméa, Nouvelle Calédonie, New Caledonia
      • Not yet recruiting
      • Centre Hospitalier Territorial Gaston-Bourret
      • Contact: Cecile CAZORLA, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Be over 18 years of age (at the time of inclusion);
• Be suspected of developing leptospirosis by the clinician in one of the 5 participating centres
• Have been informed of the use of their samples for non-therapeutic scientific research purposes by a note and information sheet established by the Institut Pasteur of New Caledonia (IPNC) and the Institut Pasteur Paris (IPP), provided and explained by the inclusion centre.
• Have expressed their oral consent to participate in this research project

Non inclusion criteria:

• Under 18 years of age
• Have not given oral consent to participate
• Have a chronic inflammatory disease.
• Having concomitant antibiotic and/or anti-inflammatory treatment or medical management incompatible with the purpose of the study,
• Pregnant or breastfeeding women.

Exclusion Criteria:

- Leptospirosis diagnostic is not confirmed by molecular biology. Complete destruction of the corresponding samples will be ensured. Clinical data and biological analyses will also be removed from the data associated with the research.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: patients diagnosed by a clinician who suspects leptospirosis	Other: Blood collection; Blood samples (8ml) at three times of the study: at baseline, 3 hours and 6 hours after treatment; Other: Data collection; collection of socio-demographic, clinical and biological data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of JHR during follow-up of patients with leptospirosis at the initiation of antibiotic therapy.	The incidence of JHR will be calculated on the total number of patients included by recording the number of participants who developed or showed an aggravation of at least one of the following clinical symptoms: Fever, tremor, chills, headache, muscle stiffness and/or pain and change in the patient's haemodynamic status (blood pressure, pulse, respiratory rate, oxygen saturation).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of JHR during leptospirosis	The description of the groups of patient with JHR will be compared to the group without JHR in terms of clinical and haemodynamic parameters Any occurrence of other unexpected clinical symptoms will be described.	1 year
Description of the administration of antibiotic treatment used for leptospirosis.	The incidence of JHR will be described on a case-by-case basis according to the antibiotic treatment (type of antibiotics, dose and mode of administration) implemented by the clinician.	1 year
Description of inflammatory markers during JHR	Description of markers of inflammation (inflammatory cytokines as TNF-α (tumor necrosis factors alpha), IL-1β, IL-10, IL-8, IL-6 (interleukines) and CRP) on patients with leptospirosis	1 year
Association of markers of inflammation with the onset of JHR.	Association of markers of inflammation (inflammatory cytokines as TNF-α, IL-1β, IL-10, IL-8, IL-6 and CRP) with the apparition of JHR on patients with leptospirosis	1 year

Collaborators and Investigators

• Sponsor: Institut Pasteur
• Investigators: Study Director: Julie CAGLIERO, PhD, Institut Pasteur de Nouvelle-Calédonie

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2021
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Actual): August 17, 2022
• Last Update Submitted That Met QC Criteria: August 16, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Spirochaetales Infections; Leptospirosis; Weil Disease
• Other Study ID Numbers: 2020-072

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No