Clinical trial NCT06627166: Viral Etiology of Severe Acute Respiratory InFection in CriticallY Ill Patients Registry
Official title: Clinical and Virological Characterization of Severe Acute Respiratory Infection Using PCR-Based Methods and Metagenomic Sequencing: a National Registry in Saudi Arabia
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Severe Acute Respiratory Infection
Keywords: SARI
Critically ill
Infection
viruses
Lead sponsor: King Abdullah International Medical Research Center
Sponsor class: OTHER
First posted: 2024-10-04
Enrollment: 13
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All eligible patients with SARI in critical care setting.

Brief summary: SARI is a major public health problem in Saudi Arabia and leads to considerable morbidity and mortality. Most SARI-related mortality occurs in patients admitted to ICUs across the country. RVIs alone and as precipitating causes of bacterial co-infections are under-recognized as causes of critical SARI. Therefore, data regarding the role of RVIs in critically ill patients with SARI in Saudi Arabia are greatly needed to fill the current gaps with respect to pathogens, disease pathogenesis, current treatment approaches, and clinical outcomes.

In the VERIFY multicenter national registry, we aim to determine the viral etiologies of SARI in mechanically ventilated critically ill patients. We aim to collect inventory samples (blood, and nasopharyngeal swabs, mini BAL) from \>10 sites in Saudi Arabia from different regions to enhance generalizability of data.

Detailed description: Data on the burden, severity and etiology of SARI amongst critically ill patients will be expected to be of a great value in guiding the prioritization of prevention and control efforts18 and in the design of future intervention studies of antivirals and other therapeutic modalities.

Because influenza is a common cause of serious respiratory illness in Saudi Arabia, although only limited data are available on the most severely ill patients with influenza, we will conduct surveillance in SARI critically ill patients and perform typing and subtyping of influenza viruses in BAL samples. We will store samples for future examination of predisposing risk factors including genetic factors.

Multiplex PCR will reduce the cost and time to detect the respiratory pathogens. In recent years, the falling costs of Whole Genome Sequencing (WGS) technologies have has proven to be a valuable tool to understand the growing threat of emerging pathogens. Metagenomic next-generation sequencing (M-NGS) has transformative effect in the last decade to investigate and understand complex microbial communities. M-NGS is simply capturing and determining all nucleic acids in a sample which allowed to identify a mixed population of microorganisms. This powerful platform simultaneously identifies genetics materials of any organisms unbiased to other methods that used specific primers to identify specific targets.

The primary objective of the VERIFY registry is to examine the virological etiologies of SARI among mechanically ventilated critically ill patients in a geographical representative sample from Saudi Arabia in order to obtain a better estimate of viral pathogen prevalence by systematic lower respiratory tract sampling and use of serology among critically ill patients in a geographical representative sample from Saudi Arabia. Contribution of viruses may be under-estimated due to the use of upper respiratory tract specimens only, and late presentation of cases to ICU (at which time antigen is no longer detectable). Therefore a systematic approach using mini-BAL to obtain lower respiratory samples will likely yield better estimate.

Eligibility criteria: Inclusion Criteria:

* Adults (≥14 years old) patients
* A clinical presentation consistent with community-acquired SARI/pneumonia
* AND admitted to the ICU because of respiratory failure or sepsis
* AND is invasively mechanically ventilated.

Exclusion Criteria:

* Diagnosed with COVID-19
* Duration of illness \> 14 days since symptom onset
* Did not meet inclusion criteria in the first 48 hrs of admission to the ICU.
* Patient already enrolled in the study
* Participant or legal guardian refuses to participate in the study.
* Diagnosis is not related to SARI
* Enrolled in interventional trial of investigational therapeutics for pneumonia.

Primary outcomes:
measure: Prevalence of different viral and bacterial pathogens among critically ill patients with SARI
timeFrame: 14 Days
Secondary outcomes:
measure: Clinical features and response to treatment of SARI of different etiologies.
timeFrame: 90 days
measure: Clinical features and response to treatment of SARI of different etiologies.
timeFrame: 90 days
measure: Clinical features and response to treatment of SARI of different etiologies.
timeFrame: 90 days
measure: Clinical features and response to treatment of SARI of different etiologies.
timeFrame: 90 days
Other outcomes:
Locations:
city: Riyadh
country: Saudi Arabia
facility: Intensive Care Department, King Abdulaziz Medical City, National Guard Health Affairs
Study officials:
affiliation: King Abdulaziz Medical City
name: Yaseen Arabi
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huai Y, Guan X, Liu S, Uyeki TM, Jiang H, Klena J, Huang J, Chen M, Peng Y, Yang H, Luo J, Zheng J, Peng Z, Huo X, Xiao L, Chen H, Zhang Y, Xing X, Feng L, Hu DJ, Yu H, Zhan F, Varma JK. Clinical characteristics and factors associated with severe acute respiratory infection and influenza among children in Jingzhou, China. Influenza Other Respir Viruses. 2017 Mar;11(2):148-156. doi: 10.1111/irv.12419. Epub 2016 Sep 20.
citation: Nguyen HKL, Nguyen SV, Nguyen AP, Hoang PMV, Le TT, Nguyen TC, Hoang HT, Vuong CD, Tran LTT, Le MQ. Surveillance of Severe Acute Respiratory Infection (SARI) for Hospitalized Patients in Northern Vietnam, 2011-2014. Jpn J Infect Dis. 2017 Sep 25;70(5):522-527. doi: 10.7883/yoken.JJID.2016.463. Epub 2017 Mar 28.
citation: Meerhoff TJ, Simaku A, Ulqinaku D, Torosyan L, Gribkova N, Shimanovich V, Chakhunashvili G, Karseladze I, Yesmagambetova A, Kuatbayeva A, Nurmatov Z, Otorbaeva D, Lupulescu E, Popovici O, Smorodintseva E, Sominina A, Holubka O, Onyshchenko O, Brown CS, Gross D. Surveillance for severe acute respiratory infections (SARI) in hospitals in the WHO European region - an exploratory analysis of risk factors for a severe outcome in influenza-positive SARI cases. BMC Infect Dis. 2015 Jan 8;15:1. doi: 10.1186/s12879-014-0722-x.
citation: Ruuskanen O, Lahti E, Jennings LC, Murdoch DR. Viral pneumonia. Lancet. 2011 Apr 9;377(9773):1264-75. doi: 10.1016/S0140-6736(10)61459-6. Epub 2011 Mar 22.