Clinical Features, Outcome and Prognosis of Human Metapneumovirus (hMPV) Lower Respiratory Tract Infections in Adult Inpatients

Lower Resp Tract Infection Clinical Trial

— French-hMPV  

Official title:

The French hMPV Study: Clinical Features, Outcome and Prognosis of Human Metapneumovirus (hMPV) Lower Respiratory Tract Infections in Adult Inpatients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03460171
• Other study ID #: HAO 17024
• Status: Active, not recruiting
• Start date: March 23, 2018
• Est. completion date: July 31, 2019

Study information

• Verified date: July 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 400
• Est. completion date: July 31, 2019
• Est. primary completion date: July 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Human Metapneumovirus Infection
• Infection
• Lower Resp Tract Infection
• Respiratory Tract Infections

Locations

Country	Name	City	State
France	Service de réanimation-Hôpital Tenon	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).		during the hospital stay or at 60 days
Secondary	Age (years)		at hospital admission
Secondary	Gender (H or F)		During the first 24 hours of ICU stay
Secondary	Height (cm)		During the first 24 hours of ICU stay
Secondary	Weight (kg)		During the first 24 hours of ICU stay
Secondary	Charlson score (points)		During the first 24 hours of ICU stay
Secondary	Presence or absence of each of the following comorbidities	smoking, asthma, COPD, chronic respiratory insufficiency requiring long term oxygen therapy, diabetes, hypertension, chronic heart failure NYHA III IV, coronary artery disease, cerebral arterial disease, chronic dialysis and cirrhosis Child Pugh B-C	During the first 24 hours of ICU stay
Secondary	Presence or absence of each of the following immunocompromised conditions	HIV infection, splenectomy, long term steroid therapy, other long term immunosuppressive drug, anticancer agents, solid organ transplant, cancer or hematologic neoplasm	During the first 24 hours of ICU stay
Secondary	Presence or absence of each of the following factors of health-care associated lower respiratory tract infection	hospitalization for = 2 days in the preceding 90 days and institutionalization	During the first 24 hours of ICU stay
Secondary	Antipneumococcal and anti-flu vaccine		During the first 24 hours of ICU stay
Secondary	Date of first respiratory symptoms (date)		During the first 24 hours of ICU stay
Secondary	Respiratory rate (maximum) during the first 24 hours of hospital stay (/min)		During the first 24 hours of ICU stay
Secondary	Temperature (maximum) during the first 24 hours of hospital stay (°C)		During the first 24 hours of ICU stay
Secondary	Heart rate (maximum) during the first 24 hours of hospital stay (/min)		During the first 24 hours of ICU stay
Secondary	Glasgow score (minimum) during the first 24 hours of hospital stay (points)		During the first 24 hours of ICU stay
Secondary	Blood leucocytes (maximum) at hospital admission (G/L)		During the first 24 hours of ICU stay
Secondary	Blood neutrophils (maximum) at hospital admission (G/L)		During the first 24 hours of ICU stay
Secondary	Blood lymphocytes (maximum) at hospital admission (G/L)		During the first 24 hours of ICU stay
Secondary	Blood platelets (maximum) at hospital admission (G/L)		During the first 24 hours of ICU stay
Secondary	Partial pressure of O2 (mmHg)		During the first 24 hours of ICU stay
Secondary	Number of quadrant with radiological abnormalities on the Chest X-Ray (number, maximum=4)		During the first 48 hours of ICU stay
Secondary	Viral co-infection		During Hospital stay, censored at 60 days
Secondary	Bacterial co-infection		During Hospital stay, censored at 60 days
Secondary	Duration of mechanical ventilation support (invasive or non invasive)		during hospital stay or at 60 days
Secondary	Shock (vasopressor support)		during hospital stay or at 60 days
Secondary	ARDS (Berlin definition)		during hospital stay or at 60 days
Secondary	Duration of ICU stay		during hospital stay or at 60 days
Secondary	Duration of hospital stay (days)		censored at 60 days
Secondary	Death		during hospital stay or at 60 days