Cohort of Patients Infected by an Arbovirus

Fever Clinical Trial

— CARBO  

Official title:

Descriptive and Prognostic Study of Arbovirus Infections in France, Based on a Hospital Cohort of Children and Adults With Suspected Arbovirose.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01099852
• Other study ID #: 09/B/08
• Status: Recruiting
• Start date: June 2010
• Est. completion date: December 2023

Study information

• Verified date: February 2023
• Source: University Hospital Center of Martinique
• Contact: Andre Cabie
• Phone: 0596552301
• Email: andre.cabie[@]chu-fortdefrance.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

There are hundred of arbovirus which have been shown to cause disease in humans. Their most common clinical symptoms are algo-eruptive (dengue, chikungunya, zika), hemorrhagic fever (dengue, yellow fever, Crimean-Congo hemorrhagic fever), neurological (West Nile, Zika, dengue, Japanese encephalitis) or arthritic afflictions (Chikungunya, O'nyong nyong). Dengue is a mosquito-born viral disease caused by 4 different serotypes of virus. Dengue fever (DF) is defined by the sudden onset of fever with non-specific constitutional symptoms, recovery occurring spontaneously in 3 to 7 days. The infection can sometimes progress to dengue hemorrhagic fever (DHF) characterized by a transient increase in vascular permeability provoking a plasma leakage syndrome. DHF can be complicated by shock and internal hemorrhage. Other rarer complications include encephalitis, hepatitis, rhabdomyolysis and myocarditis. There is currently no way of predicting the outcome of DF or DHF and the WHO classification lacks sufficient sensitivity and specificity to recognize and guide the management of severe forms of dengue. The pathophysiology of these forms is also poorly known. Since 2000s, the French West Indies and Guiana have become hyperendemic for dengue with simultaneous circulation of the 4 serotypes, regular large outbreaks and severe dengue including fatalities. Chikungunya is a re-emerging virus causing massive epidemics in Africa, in the Indian Ocean and Southeast Asia. The first autochthonous cases were described in French Antilles in Nov 2013. The disease typically consists of an acute illness like dengue fever with abrupt onset of a high-grade fever followed by constitutionals symptoms, poly-arthritis and skin involvement. Usually, the illness resolves in 4 to 6 weeks. However, severe clinical forms in early stage may appear and chronic clinical forms as incapacitating arthralgia which affect 40 to 60% of patients. In France, others arboviruses may cause severe emerging and re-emerging infectious diseases like Zika or West Nile. In non-immunized population these emerging diseases may cause outbreaks with specific severe clinical complications. The French interministerial mission on emerging infectious diseases coordinated by Professor Antoine Flahault, recommended such studies: large prospective multicenter cohort studies to characterize severe forms of arbovirus infections to seek predictive factors and to investigate the pathophysiology of the diseases.

Description:

Principal objective To identify demographic, clinical, biological, virologic, immunologic and genetic factors associated with or predictive of severe complications of arbovirus infections (shock, internal bleeding, organ failure, death) in a cohort of children and adults with confirmed arbovirus infections, in France.

Secondary objective

To identify demographic, clinical, biological, virologic, immunologic and genetic factors predictive of altered quality of life after confirmed an acute arbovirus infection. Onset of specific complications:

• Hemorrhagic fever (dengue: WHO criteria)

• Neurological disorders (West Nile virus infection, Zika virus infection, Japanese encephalitis…)

• Chronic chikungunya (persistent Chronic chikungunya (persistent musculoskeletal symptoms for more than three months after symptoms onset)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1377
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Days and older

Eligibility

INCLUSION CRITERIA :

• Adult, child or newborn with a weight > 2.5 kg the days of enrollment.

• Consulting a participating hospital center (emergency room, full hospitalization, day hospitalization, or outpatient visit).

• Arbovirosis suspected or confirmed biologically: A suspected case of arbovirus infection is defined by:

• The combination of clinical and biological signs observed suggestive of arbovirosus infection: fever (reported by the patient or family, or documented), headache, rash, myalgia, arthralgia, abdominal pain, hemorrhage, thrombocytopenia, or

• Children under 6 years: the report (by family or documented) of a fever on the day of enrollment or within 7 previous days, possibly accompanied by a of pain - At a patient with a notion of stay in 2 weeks preceding in a zone of arbovirus circulation (only for the imported cases)

A case of arbovirus infection confirmed biologically is defined by:

• RT-PCR arbovirus positive in plasma or urine (Zika virus infection), or by detection of the NS1 antigen (dengue), or an appearance or an significant increase (multiplication of the title by four) of the G immunoglobulin directed against arbovirus in question on an early taken serum (during the first week following the start of symptoms) and another taken at least 10 days later.

• Symptom onset within the 7 days before the enrollment visit or within 21 days for severe forms of the disease.Possibility of follow-up throughout study period. * Acceptance to participate in the study and in follow-up; informed consent of the patient (adult and minor in age to express his desire) or a legal representative (for minors, and patients unable to sign the consent form).

EXCLUSION CRITERIA :

• No follow-up possible after the first visit

• Patient or holder of parental authority not registered in the French medical social security national program

Related Conditions & MeSH terms

• Chikungunya
• Chikungunya Fever
• Dengue
• Fever
• Zika Virus
• Zika Virus Infection

Intervention

Other:
• biological sample collection
blood sample collection urine sample cerebrospinal fluid sample
• Quality of life Questionnaire EuroQol®
Changes in quality of life, measured with the EuroQol® questionnaire 3 and 12 weeks after the onset of dengue fever symptoms.
• Health Assessment Questionnaire - MDHAQ and RAPID3
Questionnaire used at the 3rd month of follow up.
• Neuropathic Pain Questionnaire (DN4)
Questionnaire used during the follow up

Locations

Country	Name	City	State
France	Hôpital Saint André	Bordeaux
France	Hôpital Bichat-Claude Bernard	Paris
France	Hôpital La Pitié Salpêtrière	Paris
French Guiana	CH André Rosemond	Cayenne
Guadeloupe	CHU de Pointe à Pitre/Abymes	Pointe à Pitre
Martinique	Centre Hospitalier Universitaire de Martinique	Fort-de-France
Réunion	CHU de la Réunion	Saint-Denis
Réunion	Centre Hospitalier Gabriel Martin	Saint-Paul

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital Center of Martinique	Clinique Antilles-Guyane, Institut National de la Santé Et de la Recherche Médicale, France

Countries where clinical trial is conducted

France,  French Guiana,  Guadeloupe,  Martinique,  Réunion, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence, during follow-up (for 12 weeks following symptom onset), of shock, internal bleeding, failure of one or several organs or systems (brain, heart, lung, liver, kidney, clotting system), or death.	The primary endpoint is a composite endpoint defined as the occurrence, within 12 weeks of the onset of arbovirosis, of at least 1 of the following events: death or shock or internal bleeding, or failure to one or more organs or systems (brain, heart, lung, liver, kidney, hemostasis). Deaths not attributable directly or indirectly to the arbovirosis in question will not be taken into account.	12 weeks
Secondary	Specific complications: Onset of hemorrhagic fever (dengue) Onset of encephalitis or neurological disorders (West Nile virus, Japanese encephalitis, Zika virus) Onset of chronic form (Chikungunya)	The analysis will focus only on patients with biologically confirmed arbovirosis by one of the following exams: RT-PCR plasma (arbovirus), or urine (Zika virus),; Research of the NS1 positive antigen (dengue),; Significant appearance or increase of the G immunoglobulin directed against the arbovirus in question between an early serum (during the first week following the onset of symptoms) and another taken at least 10 days later	12 weeks