Longitudinal Recovery Trajectories After an Acute Respiratory Distress Syndrome, a New Understanding

ARDS Clinical Trial

— TENACITY  

Official title:

Longitudinal Recovery Trajectories After an Acute Respiratory Distress Syndrome, a New Understanding. The TENACITY Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06083363
• Other study ID #: PI23/01381
• Status: Recruiting
• Start date: June 29, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2024
• Source: Institut de Recerca Biomèdica de Lleida
• Contact: Jessica González Gutiérrez, MD, PhD
• Phone: 973 70 53 72
• Email: jgonzalezgutierrez88[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

COVID-19 resulted in the largest cohort of critical illness survivors in history, heightened awareness of the importance of the respiratory sequelae after an acute distress respiratory syndrome (ADRS). Despite the advancement of acute-phase ARDS management, it is unknown whether there are differences in the longitudinal recovery trajectories between patients with post-ARDS due to COVID-19 and due to other causes. The main objective of the study is to identify risk factors of pulmonary sequela (lung diffusing capacity) at long-term follow-up in survivors of ARDS. The investigators are also interested in describing the long-term longitudinal recovery trajectories at a multi-dimensional level (symptoms, quality of life, neurocognitive, other lung function parameters, exercise capacity, chest imaging and molecular profiles) of ARDS survivors, and compared between ARDS caused by COVID-19. The ultimate goal is to understand the pathobiological mechanisms associated with a severe lung injury at the long term, allowing the introduction of clinical guidelines for the management of post-ARDS patients and the assignment of personalized interventions.

Description:

The coronavirus disease 2019 (COVID-19) resulted in the largest cohort of critical illness survivors in history, heightened awareness of the importance of the multi-dimensional sequelae after an acute distress respiratory syndrome (ADRS). With the advancement of acute-phase ARDS management, it is unknown whether there are differences in longitudinal recovery trajectories in terms of lung function, symptoms, quality of life, neurocognitive disorders, exercise capacity, chest imaging, and even at molecular basis between patients with post-ARDS due to COVID-19 and due to other causes. This project will continue to generate information about non-COVID-19 post-ARDS based on the experience in our post-COVID consultation that began in May 2020.

The main objective of the study is to identify risk factors of pulmonary sequela in terms of DLCO at long-term follow-up in survivors of ARDS. The investigators are also interested in describing the long-term longitudinal recovery trajectories at a multidimensional level (symptoms, quality of life, neurocognitive, other lung function parameters, exercise capacity, chest imaging and molecular profiles) of ARDS survivors. Furthermore, risk factors as well as recovery trajectories will be compared between ARDS caused by COVID-19 and non-COVID-19. The ultimate goal is to understand the pathobiological mechanisms associated with a severe lung injury at the long term (one year after hospital discharge), in order to provide novel therapeutic targets to develop future intervention studies.

For doing so, adult ARDS survivors of any origin (different than COVID-19) (n=246) referred to the post-CRITICAL consultation at the University Hospitals of Arnau de Vilanova and Santa Maria (Lleida), University Hospital Joan XXIII (Tarragona) and Verge de la Cinta (Tortosa) will be included in this multicentric, prospective, longitudinal and observational study. Previous standardized protocol will be followed at 3, 6 and 12 months after hospital discharge with a complete evaluation of symptoms, neurocognitive, memory problems and quality of life. Lung function, exercise test, chest CT and molecular analysis will be performed at each time point. The prognostic factors and the longitudinal recovery trajectories of ARDS survivors will be assessed using latent class mixed and machine learning artificial models.

The specific objectives to achieve the general objective are the following:

• Objective 1: To identify risk factors of lung function sequelae (spirometry, total lung volumes and lung diffusing capacity) in non-COVID-19 ARDS survivors.

• Objective 2: To identify risk factors of structural pulmonary sequelae (chest CT findings) in non-COVID-19 ARDS survivors.

• Objective 3: To identify risk factors of symptoms, neurocognitive disorders (BC-CCI, MOCA) and quality of life (SF-12) in non-COVID-19 ARDS survivors.

• Objective 4: To develop a clinical scoring tool to predict pulmonary sequelae at short- and long-term follow-up.

• Objective 5: To compare risk factors and recovery trajectories with COVID-19 ARDS survivors using data previously collected.

• Objective 6: To use artificial intelligence to identify multidimensional phenotypes associated with recovery trajectories.

• Objective 7: To design a cost-effective follow-up plan after hospital discharge in ARDS patients based on hospital risk factors.

• Objective 8: To identify molecular profiles according to recovery trajectories in non-COVID-19 ARDS.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 246
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male and female patients aged =18 years

• Admission to the ICU

• Diagnosis of severe pneumonia and/or diagnosis of acute respiratory distress syndrome (ARDS) based on the 2023 definition due to any origin (infectious and non-infectious)

Exclusion Criteria:

• Life expectancy less than a year

• Transfer to another hospital during hospitalization or follow-up

• Stay in palliative care

• Severe mental disability that makes it impossible to carry out pulmonary function tests during follow-up

Related Conditions & MeSH terms

• Acute Lung Injury
• ARDS
• Disease Progression
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn

Locations

Country	Name	City	State
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Hospital Universitari Joan XXIII	Tarragona
Spain	Hospital de Tortosa Verge de la Cinta	Tortosa	Tarragona

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recerca Biomèdica de Lleida	Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in lung diffusing capacity	Changes in the results of lung diffusing capacity (DLCO) in terms of mL/mmHg/MI	3, 6 and 12 months
Primary	Changes in lung diffusing capacity	Changes in the results of lung diffusing capacity (DLCO) in terms of percentage (%)	3, 6 and 12 months
Primary	Changes in lung volumes	Changes in the results of lung capacity or total lung capacity (TLC) in terms of Liters (L)	3, 6 and 12 months
Primary	Changes in lung volumes	Changes in the results of lung capacity or total lung capacity (TLC) in terms of percentage (%)	3, 6 and 12 months
Primary	Changes in chest CT findings	Identification of structural pulmonary sequelae in terms of chest CT findings	3, 6 and 12 months
Secondary	Changes in the perceived cognitive difficulties	Changes in the results of the British Columbia Cognitive Complaints Inventory (BC-CCI) test.; The scale consists of 6 items assessing perceived problems with concentration, memory, expressing thoughts, word finding, slow thinking, and difficulty solving problems in the past 7 days. Scores on each item (ranging from 0, not at all, to 3, very much) are summed to yield a total score ranging from 0 to 18; higher scores indicate greater severity of cognitive complaints.	3, 6 and 12 months
Secondary	Changes in the cognitive function	Changes in the results of Montreal Cognitive Assessment (MoCA) test.; The MoCA test examines seven domains of cognitive function with a total of 11 different exercises and tasks. The total score ranges from 0 to 30, lower scores indicate greater severity of cognitive impairment.	3, 6 and 12 months
Secondary	Changes in the fatigue status	Changes in the results of Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (Version 4); This scale is a short test of 13-item that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The total score range is 0-52, being the higher the score, the better the quality of life and less perception of fatigue.	3, 6 and 12 months
Secondary	Changes in the levels of anxiety	Changes in the results of Hospital Anxiety and Depression Scale (HAD); The scale determines the levels of anxiety and depression that a person is experiencing. It is a 14 item scale (7 of the items relate to anxiety and 7 relate to depression). Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. Lower scores indicate less anxiety or depression.	3, 6 and 12 months
Secondary	Changes in independence to carry out daily activities	Changes in the results of Barthel test.; Barthel Index (BI) measures the extent to which somebody can function independently and has mobility in their activities of daily living. The Index yields a total score out of 100 - the higher the score, the greater the degree of functional independence. This score is calculated by simply totaling the individual item scores.	3, 6 and 12 months
Secondary	Changes in the perception of life quality	Changes in the results of 12-Item Short Form Survey (SF-12) test.; The SF-12 is a self-reported outcome measure composed by 12 items which examine eight dimensions of physical and mental health. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning.	3, 6 and 12 months
Secondary	Validation of a clinical scoring tool	Validation of a clinical scoring tool to predict pulmonary sequelae at short- and long-term follow-up.	3, 6 and 12 months
Secondary	Cost-effectiveness of a follow-up plan	Only direct costs will be considered. Analysis will include an estimation of quality-adjusted life-years (QALYs) gained	3, 6 and 12 months
Secondary	Identification of molecular profiles	Classification of the population in different molecular profiles according to their recovery trajectories	3, 6 and 12 months
Secondary	Multidimensional phenotypes	multidimensional phenotypes associated with recovery trajectories defined with artificial intelligence	3, 6 and 12 months
Secondary	Recovery trajectories of lung diffusing capacity	Comparison of risk factors and recovery trajectories in terms of lung diffusing capacity (DLCO) with COVID-19 ARDS survivors using data previously collected.	3, 6 and 12 months
Secondary	Recovery trajectories of total lung capacity	Comparison of risk factors and recovery trajectories in terms of total lung capacity (TLC) with COVID-19 ARDS survivors using data previously collected.	3, 6 and 12 months
Secondary	Recovery trajectories of perception of life quality	Comparison of risk factors and recovery trajectories in terms of perception of life quality (SF12 test) with COVID-19 ARDS survivors using data previously collected.	3, 6 and 12 months
Secondary	Recovery trajectories of perception of fatigue	Comparison of risk factors and recovery trajectories in terms of perception of fatigue (FACIT-4 test) with COVID-19 ARDS survivors using data previously collected.	3, 6 and 12 months