Clinical trial NCT03460171: Clinical Features, Outcome and Prognosis of Human Metapneumovirus (hMPV) Lower Respiratory Tract Infections in Adult Inpatients
Official title: The French hMPV Study: Clinical Features, Outcome and Prognosis of Human Metapneumovirus (hMPV) Lower Respiratory Tract Infections in Adult Inpatients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lower Resp Tract Infection
Human Metapneumovirus Infection
Keywords: Human Metapneumovirus
Paramyxoviridae infections
Lower-respiratory tract infections
Pneumonia
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-03-09
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All consecutive adult patients admitted to hospital with an acute lower respiratory tract infection and a respiratory MPCR positive for hMPV.

Participating centres are respiratory diseases departments, infectious diseases departments and intensive care units of secondary and tertiary care hospitals in France.

Brief summary: The human metapneumovirus (hMPV) was first described in 2001. It belongs to the paramyxovirus family and is genetically close to the Respiratory Syncytial Virus (RSV). hMPV has a seasonal epidemic pattern, between January to April. Clinical symptoms of hMPV infection include influenza-like illness (fever, asthenia and curvatures) associated with signs of respiratory tract infection. The incidence of hMPV infection is higher in children than in adults. In child pneumonia, hMPV is the third most frequent isolated pathogen (14 % of the subjects), after rhinovirus and RSV. In hospitalized adults, hMPV was detected in 6 to 8% of the subjects with lower respiratory tract and in 4 % of subjects with pneumonia.

Clinical, radiological and biological features, as well as evolution course of hMPV infections have been mainly described in children. Clinical presentation of in adult seems polymorph, ranging from acute bronchitis or exacerbation of COPD to pneumonia. The frequency of viral-bacterial coinfection is unknown. Intensive care unit (ICU) admission may involve almost 1 for 10 patients. Elderly and immunocompromised subjects are probably high-risk subjects.

Currently, treatment of hMPV infections is mainly symptomatic. However, several anti-RSV drugs that are currently in clinical development have demonstrated an activity against other paramyxoviridae in pre-clinical studies. Consequently, it seems necessary to better characterize hMPV infections in adult inpatients: presentation, course profile and risk factors for morbidity and mortality. These data would help clinicians to identify high risk patients, and consequently to choose those who could benefit from coming treatments.

The French hMPV Study is observational prospective multicenter clinical study. The study population includes all consecutive adult inpatients with a community-acquired acute lower respiratory tract infection and a mPCR positive for hMPV on any respiratory sample. The primary objective is to describe the prognosis. The secondary objectives are i) to characterize clinical, radiological and biological features, ii) to describe the hospital course and the rate of ICU transfer; in ICU patients, to describe organ failures and supports, and iii) to describe the viral and/or bacterial coinfections. The primary endpoint is the number of subjects with a poor outcome (defined by the requirement for invasive mechanical ventilation and/or the death during the hospital stay).

Detailed description: The human metapneumovirus (hMPV) was first described in 2001. It belongs to the paramyxovirus family (paramyxoviridae subfamily). hMPV is genetically close to the Respiratory Syncytial Virus (RSV). hMPV has a seasonal epidemic pattern, between January to April. Incubation period varies between 4 and 6 days. Clinical symptoms of hMPV infection are close to that of RSV, with influenza-like illness (fever, asthenia and curvatures) associated with signs of upper and/or lower respiratory tracts infection. The incidence of hMPV infection is higher in children than in adults. In a large cohort of children with respiratory illness or fever, hMPV was detected in 7 % of outpatients and 6 % of hospitalized children. The annual rate of hospitalization associated with hMPV infection has been estimated about 1 per 1000 children less than 5 years of age. In child pneumonia, hMPV is the third most frequent isolated pathogen (14 % of the subjects), after rhinovirus and RSV. In hospitalized adults, hMPV was detect in 6 to 8% of the subjects with a lower respiratory tract and in 4 % of subjects with a pneumonia.

Clinical, radiological and biological features, as well as evolution course of hMPV-associated infections have been mainly described in children. Clinical presentation of hMPV-associated infection in adult seems polymorph, ranging from acute bronchitis or exacerbation of chronic pulmonary diseases (COPD and asthma) to pneumonia. Viral-viral coinfections are not exceptional whereas the frequency of viral-bacterial coinfection is unknown. Intensive care unit (ICU) admission involved almost 1 for 10 patients. Elderly and immunocompromised subjects are probably high-risk subjects. Only one cohort of hMPV-infected patients admitted to ICU has been reported. Among the 40 patients, 6 were non-immunocompromised and without comorbidity. Factors associated with a poor prognosis were not studied.

Currently, treatment of hMPV-associated lower respiratory tract infections is mainly symptomatic. However, several anti-RSV drugs that are currently in clinical development in humans, have demonstrated an activity against other paramyxoviridae (hMPV and parainfluenza virus) in pre-clinical studies. These anti-RSV drugs should be available for clinicians in the next few years. Considering their activity against other paramyxoviridae, clinicians will probably attempt to use these anti-RSV drugs in non-RSV paramyxoviridae-associated lower respiratory tracts infections in adult inpatients. Consequently, it seems necessary to better characterize hMPV-associated lower respiratory tracts infections in adult inpatients: clinical, radiological and biological presentation, course profile and risk factors for morbidity and mortality. These data would help clinicians to identify high risk patients, and consequently to choose those who could benefit from coming treatments.

The French hMPV Study is observational prospective multicenter clinical study. The study population includes all consecutive adult inpatients with a community-acquired acute lower respiratory tract infection and a mPCR positive for hMPV on any respiratory sample. The primary objective is to describe the prognosis. The secondary objectives are i) to characterize the clinical (time from onset to hospital admission, general symptoms, respiratory symptoms and signs), radiological and biological features, ii) to describe the hospital course and the rate of ICU transfer; in ICU patients, to describe organ failures and supports, and iii) to describe the viral and/or bacterial coinfections.

Eligibility criteria: Inclusion Criteria:

* Adult (≥18 years old) inpatients with:
* an acute lower respiratory tract infection, defined by the presence of two of the following criteria in the 5 days preceding hospital admission or during the present hospital stay : fever, cough, expectoration, exercise or rest dyspnea, crackles, tubal breath, signs of respiratory failure (respiratory rate higher than 30 per minute...), thoracic pain, oxygen therapy, mechanical ventilation;
* a respiratory mPCR (upper respiratory tracts specimen such as nasopharyngeal swab or lower respiratory tract specimen such as tracheal or bronchial aspiration or bronchoalveolar lavage) positive for hMPV in the 5 days following hospital admission.

Exclusion Criteria:

* Patient already included in the study.

Primary outcomes:
measure: The primary endpoint is the number of subjects with a poor outcome (defined by the requirement for invasive mechanical ventilation and/or the death during the hospital stay or at 60 days).
timeFrame: during the hospital stay or at 60 days
Secondary outcomes:
measure: Age (years)
timeFrame: at hospital admission
measure: Gender (H or F)
timeFrame: During the first 24 hours of ICU stay
measure: Height (cm)
timeFrame: During the first 24 hours of ICU stay
measure: Weight (kg)
timeFrame: During the first 24 hours of ICU stay
measure: Charlson score (points)
timeFrame: During the first 24 hours of ICU stay
measure: Presence or absence of each of the following comorbidities
timeFrame: During the first 24 hours of ICU stay
measure: Presence or absence of each of the following immunocompromised conditions
timeFrame: During the first 24 hours of ICU stay
measure: Presence or absence of each of the following factors of health-care associated lower respiratory tract infection
timeFrame: During the first 24 hours of ICU stay
measure: Antipneumococcal and anti-flu vaccine
timeFrame: During the first 24 hours of ICU stay
measure: Date of first respiratory symptoms (date)
timeFrame: During the first 24 hours of ICU stay
measure: Respiratory rate (maximum) during the first 24 hours of hospital stay (/min)
timeFrame: During the first 24 hours of ICU stay
measure: Temperature (maximum) during the first 24 hours of hospital stay (°C)
timeFrame: During the first 24 hours of ICU stay
measure: Heart rate (maximum) during the first 24 hours of hospital stay (/min)
timeFrame: During the first 24 hours of ICU stay
measure: Glasgow score (minimum) during the first 24 hours of hospital stay (points)
timeFrame: During the first 24 hours of ICU stay
measure: Blood leucocytes (maximum) at hospital admission (G/L)
timeFrame: During the first 24 hours of ICU stay
measure: Blood neutrophils (maximum) at hospital admission (G/L)
timeFrame: During the first 24 hours of ICU stay
measure: Blood lymphocytes (maximum) at hospital admission (G/L)
timeFrame: During the first 24 hours of ICU stay
measure: Blood platelets (maximum) at hospital admission (G/L)
timeFrame: During the first 24 hours of ICU stay
measure: Partial pressure of O2 (mmHg)
timeFrame: During the first 24 hours of ICU stay
measure: Number of quadrant with radiological abnormalities on the Chest X-Ray (number, maximum=4)
timeFrame: During the first 48 hours of ICU stay
measure: Viral co-infection
timeFrame: During Hospital stay, censored at 60 days
measure: Bacterial co-infection
timeFrame: During Hospital stay, censored at 60 days
measure: Duration of mechanical ventilation support (invasive or non invasive)
timeFrame: during hospital stay or at 60 days
measure: Shock (vasopressor support)
timeFrame: during hospital stay or at 60 days
measure: ARDS (Berlin definition)
timeFrame: during hospital stay or at 60 days
measure: Duration of ICU stay
timeFrame: during hospital stay or at 60 days
measure: Duration of hospital stay (days)
timeFrame: censored at 60 days
measure: Death
timeFrame: during hospital stay or at 60 days
Other outcomes:
Locations:
city: Paris
country: France
facility: Service de réanimation-Hôpital Tenon
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Guillaume Voiriot, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Muriel Fartoukh, MD PhD
role: STUDY_DIRECTOR
References: