Practice of Ventilation in Middle-Income Countries

Mechanical Ventilation Clinical Trial

— PRoVENT-iMIC  

Official title:

PRactice of VENTilation in Critically Ill Patients in Middle-Income Countries (PRoVENT-iMIC) - an International Multicenter Service Review Focusing on ICUs in Asia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03188770
• Other study ID #: PRoVENT-iMIC
• Status: Completed
• Start date: November 1, 2017
• Est. completion date: January 29, 2019

Study information

• Verified date: July 2019
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this international, multicenter service review is to describe and compare ventilation management in patients at risk of acute respiratory distress syndrome (ARDS) versus patients not at risk and patients with established ARDS, and to ascertain whether certain ventilator settings and ventilation parameters are associated with pulmonary complications or development of ARDS after start of ventilation in patients in intensive care units (ICUs) in Asian countries.

Participating centers will include adult patients undergoing mechanical ventilation in the ICU during a 28-day period. Patients' data will be collected during the first 7 days in the ICU, or until ICU discharge. Follow up is until ICU discharge. The primary outcome includes two main ventilator settings, i.e., tidal volume and the level of positive end-expiratory pressure. Secondary endpoints are development of ARDS in patients without ARDS at the onset of mechanical ventilation, worsening of ARDS in patients with ARDS at the onset of mechanical ventilation, pulmonary infection, other pulmonary complications, need for tracheostomy, duration of ventilation, length of ICU stay and ICU mortality.

Description:

Rationale: scarce information exists on management of mechanical ventilation in intensive care unit (ICU) patients in low- and middle-income countries.

Objective:The primary objective is to describe and compare ventilation management in patients at risk of ARDS versus individuals not at risk, and patients with established ARDS, and to ascertain whether certain ventilation settings are associated with a higher incidence of developing ARDS in patients in ICUs in Asia. PRoVENT-iMIC secondary objectives are to determine the epidemiological characteristics and clinical outcomes of patients at risk of ARDS in ICUs in Asia according to the ventilation practice applied.

Primary hypothesis: a large proportion of patients at risk of ARDS in ICUs in Asia do not receive so-called protective ventilation, defined as tidal volume < 8 ml/kg predicted body weight and a level of positive end-expiratory pressure of at least 5 cm H2O.

Secondary hypothesis: in ICUs in Asia a large proportion of patients is at risk of ARDS, as stratified by a Lung Injury Prediction Score of ≥4.

Study design: an international multicenter service review focusing on ICUs in selected middle-income Asian countries.

Population: consecutive intubated and ventilated ICU patients.

Methods: Patients in participating ICUs will be screened daily during a 28-day period. A registry of limited demographic data will be compiled on all screened patients. Collection of ventilation characteristics is restricted to the first three days. The first seven days or up to death, whichever comes first, will be used for collection of patient demographics (on day of admission), development of ARDS and other pulmonary complications. All patients will be followed until ICU-discharge to determine length of stay in ICU and ICU mortality. The inclusion period will be flexible for participating centers and determined at a later stage together with the study-coordinator. Data will be coded by a patient identification number of which the code will be kept safe at the local sites. The data will be transcribed by local investigators onto an internet based electronic case report form (https://www.project-redcap.org).

Centers: about 60 Asian ICUs from ten countries are expected to participate in this international multicenter study. Each participating center will recruit ~ 50 patients.

Ethics Approval: The Oxford Tropical Research Ethical Committee has evaluated the study and considered it exempt from ethical review on the 1st of June 2017. National coordinators will be responsible for clarifying the need for ethics approval and applying for this where appropriate according to local policy. Centers will not be permitted to record data unless ethics approval or an equivalent waiver is in place.

Monitoring: Due to the observational nature of the study, a Data Safety and Monitoring Board is not necessary.

Sample Size Calculation: a formal sample size calculation was not performed, seen the largely descriptive character of this investigation. 3000 patients are expected to be enrolled in the study period, which will be sufficient to test the hypotheses.

Statistical Analysis: Patient characteristics will be compared and described by appropriate statistics. Student's t-test or Mann-Whitney U-tests are used to compare continuous variables and chi-squared tests are used for categorical variables. Data are expressed as means (SD), medians (interquartile range) and proportions as appropriate. Comparisons between and within groups are performed using one-way ANOVA and post-hoc analyses for continuous variables.

The primary analysis concerns the determination of (variation of) tidal volume and PEEP levels in patients without ARDS. These are compared between predefined patient groups: patients at no risk for ARDS, patients at risk for ARDS, patients with mild ARDS, and patients with moderate or severe ARDS.

To identify potential factors associated with outcome like development of ARDS, or worsening of ARDS, development of pulmonary complications, duration of ventilation, or death, univariate analyses are performed. A multivariate logistic regression model is used to identify independent risk factors. A stepwise approach is used to enter new terms into the model, with a limit of p < 0.2 to enter the terms. Time to event variables are analyzed using Cox regression and visualized by Kaplan-Meier.

Organization: The study is conducted by the PROtective VEntilation Network (PROVENet). National co-ordinators will lead the project within individual nations and identify participating hospitals, translate study paperwork, distribute study paperwork and ensure necessary regulatory approvals are in place. They provide assistance to the participating clinical sites in trial management, record keeping and data management. Local coordinators in each site will supervise data collection and ensure adherence to Good Clinical Practice during the trial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1315
• Est. completion date: January 29, 2019
• Est. primary completion date: November 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Admitted to an ICU participating in this study

• Intubated in the ICU, or in the emergency room, general ward, or operation room before the present ICU admission

Exclusion Criteria:

• Age < 18 years

• Patients under invasive mechanical ventilation previous to the 28-day period of inclusion

• Patients transferred from another hospital under invasive mechanical ventilation

• Receiving only non-invasive ventilation (i.e., patient never received invasive ventilation during the present admission)

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Failure
• Mechanical Ventilation
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Respiratory Insufficiency

Locations

Country	Name	City	State
Bangladesh	Chittagong Medical College Hospital	Chittagong
Bangladesh	Bangabandhu Sheikh Mujib Medical University	Dhaka
Bangladesh	BIRDEM General Hospital	Dhaka
Bangladesh	Dhaka Medical College Hospital	Dhaka
Bangladesh	Rajshahi Medical College Hospital	Rajshahi
Bangladesh	Sylhet MAG Osmani Medical College Hospital	Sylhet
India	St. John's Medical College	Bangalore
India	Bharati Vidyapeeth Medical College	Pune
India	Ispat General Hospital	Raurkela	Odisha
Iran, Islamic Republic of	Masih Daneshvari Hospital	Tehran
Iran, Islamic Republic of	Modarres Hospital	Tehran
Iran, Islamic Republic of	Pars Hospital	Tehran
Malaysia	Monash University	Johor Bahru
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	Mohamad Irfan Bin Othman Jailani	Kuala Lumpur
Malaysia	International Islamic University Medical Center	Kuantan
Maldives	Indira Gandhi Memorial Hospital	Malè
Nepal	Patan Academy of Health Sciences	Katmandou
Pakistan	Allied Hospital	Faisalabad
Pakistan	PIMS	Islamabad
Pakistan	Shifa International Hospital	Islamabad
Pakistan	Aga Khan University Hospital MICU	Karachi
Pakistan	Aga Khan University SICU	Karachi
Pakistan	Patel Hospital	Karachi
Pakistan	Doctor's Hospital	Lahore
Pakistan	National Hospital and Medical Center	Lahore
Pakistan	Peoples Medical College Hospital	Nawabshah
Pakistan	North West General Hospital	Peshawar
Sri Lanka	Batticaloa Base Hospital	Batticaloa
Sri Lanka	Colombo South Teaching Hospital MICU	Colombo
Sri Lanka	Colombo South Teaching Hospital SICU	Colombo
Sri Lanka	Lanka Hospital	Colombo
Sri Lanka	National Hospital Sri Lanka MICU	Colombo
Sri Lanka	National Hospital Sri Lanka SICU	Colombo
Sri Lanka	Sri Jayawardenepura CTICU	Colombo
Sri Lanka	Sri Jayewardenepura General Hospital GICU	Colombo
Sri Lanka	Karapitiya Teaching Hospital	Galle
Sri Lanka	Jaffna Teaching Hospital	Jaffna
Sri Lanka	Puttlam Hospital	Puttalam
Thailand	Chulalongkorn University Hospital	Bangkok
Thailand	Hospital for Tropical Diseases, Mahidol University	Bangkok
Thailand	Ramathibodi Hospital	Bangkok
Thailand	Sriraj Hospital	Bangkok
Thailand	Vajira Hospital	Bangkok
Thailand	Chiang Mai Hospital Surgical ICU	Chiang Mai
Thailand	Chiang Mai Medical ICU	Chiang Mai
Thailand	Nakornping Hospital	Chiang Mai
Thailand	Prince of Songkla University	Hat Yai
Thailand	Srinakharinwirot University	Ongkharak
Vietnam	National Hospital for Tropical Diseases	Hanoi
Vietnam	Oxford University Clinical Research Unit	Ho Chi Minh City

Sponsors (3)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	Hospital Israelita Albert Einstein, Mahidol Oxford Tropical Medicine Research Unit

Countries where clinical trial is conducted

Bangladesh,  India,  Iran, Islamic Republic of,  Malaysia,  Maldives,  Nepal,  Pakistan,  Sri Lanka,  Thailand,  Vietnam, 

References & Publications (2)

Neto AS, Barbas CSV, Simonis FD, Artigas-Raventós A, Canet J, Determann RM, Anstey J, Hedenstierna G, Hemmes SNT, Hermans G, Hiesmayr M, Hollmann MW, Jaber S, Martin-Loeches I, Mills GH, Pearse RM, Putensen C, Schmid W, Severgnini P, Smith R, Treschan TA, — View Citation

Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Espósito DC, Pasqualucci Mde O, Damasceno MC, Schultz MJ. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012 Oct 24;308(16):1651-9. doi: 10.1001/jama.2012.13730. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tidal volume size	Tidal volume size in milliliters per kilogram of predicted body weight	Day 1 to Day 3 from initiation of mechanical ventilation
Primary	Positive end-expiratory pressure	Pressure in cm of water	Day 1 to Day 3 from initiation of mechanical ventilation
Secondary	Patients at risk of ARDS	Risk of ARDS is stratified using the Lung Injury Prediction Score.	On the date of inclusion
Secondary	Inspired Oxygen Concentration	expressed as fraction of inspired oxygen	Day 1 to Day 3 from initiation of mechanical ventilation
Secondary	Plateau pressure	Pressure in cm of water	Day 1 to Day 3 from initiation of mechanical ventilation
Secondary	Peak pressure	Peak away pressure in cm of water	Day 1 to Day 3 from initiation of mechanical ventilation
Secondary	Driving pressure	pressure in cm of water	Day 1 to Day 3 from initiation of mechanical ventilation
Secondary	Respiratory Rate	in breaths per minute	Day 1 to Day 3 from initiation of mechanical ventilation
Secondary	Minute Volume	expressed as liters per minute	Day 1 to Day 3 from initiation of mechanical ventilation
Secondary	Development of ARDS	Development of ARDS in patients without ARDS at the onset of mechanical ventilation. Patients are defined as having ARDS if they meet the Berlin criteria for ARDS	From date of inclusion until the date of first documented development of ARDS or date of ICU discharge or death from any cause, whichever came first, assessed up to 7 days
Secondary	Worsening of ARDS	Defined as any worsening in the degree of severity according to Berlin criteria.	From date of inclusion until the date of first documented worsening of ARDS or date of ICU discharge or death from any cause, whichever came first, assessed up to 7 days
Secondary	Pulmonary infection	defined as need of new antibiotics in the presence of new or changed lung opacities on chest X-ray and/or new or changed sputum plus at least one of the following criteria: 1) temperature > 38.3 ºC; or 2) WBC count > 12,000	From date of inclusion until the date of first documented pulmonary complication or date of ICU discharge or death from any cause, whichever came first, assessed up to 7 days
Secondary	Other Pulmonary complications	pneumothorax, pleural effusions, cardiogenic pulmonary edema, new pulmonary infiltrates, and atelectasis	From date of inclusion until the date of first documented pulmonary complication or date of ICU discharge or death from any cause, whichever came first, assessed up to 7 days
Secondary	Need for tracheostomy	Need for tracheostomy during ICU stay	From date of inclusion until the date of first documented tracheostomy procedure or date of ICU discharge or death from any cause, whichever came first, assessed up to 7 days
Secondary	Length of stay in ICU	Time between admission and discharge or death	Until day 35 from study initiation
Secondary	All-cause ICU mortality	Any death during ICU stay	Until day 35 from study initiation
Secondary	Duration of mechanical ventilation	time between orotracheal intubation and successful extubation;note: in case of intermittent MV via a tracheostomy, every day a patient needs MV counts as one extra day of MV, irrespective of duration of MV that specific day; in case of non-invasive ventilation (CPAP and/or BIPAP), the duration will be assessed separated from the assessment of invasive mechanical ventilation.	Until day 35 from study initiation

External Links

•   Protective Ventilation Network website
•   Study website