Clinical trial NCT03188770: Practice of Ventilation in Middle-Income Countries
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Mechanical Ventilation
Respiratory Distress Syndrome, Adult
Acute Respiratory Failure
Keywords: Middle-income countries
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Mahidol Oxford Tropical Medicine Research Unit
name: Hospital Israelita Albert Einstein
First posted: 2017-06-15
Enrollment: 1315
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: consecutive intubated and ventilated intensive care unit patients

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Tidal volume size
timeFrame: Day 1 to Day 3 from initiation of mechanical ventilation
measure: Positive end-expiratory pressure
timeFrame: Day 1 to Day 3 from initiation of mechanical ventilation
Secondary outcomes:
measure: Patients at risk of ARDS
timeFrame: On the date of inclusion
measure: Inspired Oxygen Concentration
timeFrame: Day 1 to Day 3 from initiation of mechanical ventilation
measure: Plateau pressure
timeFrame: Day 1 to Day 3 from initiation of mechanical ventilation
measure: Peak pressure
timeFrame: Day 1 to Day 3 from initiation of mechanical ventilation
measure: Driving pressure
timeFrame: Day 1 to Day 3 from initiation of mechanical ventilation
measure: Respiratory Rate
timeFrame: Day 1 to Day 3 from initiation of mechanical ventilation
measure: Minute Volume
timeFrame: Day 1 to Day 3 from initiation of mechanical ventilation
measure: Development of ARDS
timeFrame: 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
measure: Worsening of ARDS
timeFrame: 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
measure: Pulmonary infection
timeFrame: 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
measure: Other Pulmonary complications
timeFrame: 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
measure: Need for tracheostomy
timeFrame: 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
measure: Length of stay in ICU
timeFrame: Until day 35 from study initiation
measure: All-cause ICU mortality
timeFrame: Until day 35 from study initiation
measure: Duration of mechanical ventilation
timeFrame: Until day 35 from study initiation
Other outcomes:
Locations:
city: Chittagong
country: Bangladesh
facility: Chittagong Medical College Hospital
city: Dhaka
country: Bangladesh
facility: Bangabandhu Sheikh Mujib Medical University
city: Dhaka
country: Bangladesh
facility: BIRDEM General Hospital
city: Dhaka
country: Bangladesh
facility: Dhaka Medical College Hospital
city: Rajshahi
country: Bangladesh
facility: Rajshahi Medical College Hospital
city: Sylhet
country: Bangladesh
facility: Sylhet MAG Osmani Medical College Hospital
city: Raurkela
country: India
facility: Ispat General Hospital
state: Odisha
city: Bangalore
country: India
facility: St. John's Medical College
city: Pune
country: India
facility: Bharati Vidyapeeth Medical College
city: Tehran
country: Iran, Islamic Republic of
facility: Modarres Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Pars Hospital
city: Tehrān
country: Iran, Islamic Republic of
facility: Masih Daneshvari Hospital
city: Johor Bahru
country: Malaysia
facility: Monash University
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuala Lumpur
country: Malaysia
facility: Mohamad Irfan Bin Othman Jailani
city: Kuantan
country: Malaysia
facility: International Islamic University Medical Center
city: Malè
country: Maldives
facility: Indira Gandhi Memorial Hospital
city: Katmandou
country: Nepal
facility: Patan Academy of Health Sciences
city: Faisalābad
country: Pakistan
facility: Allied Hospital
city: Islamabad
country: Pakistan
facility: PIMS
city: Islamabad
country: Pakistan
facility: Shifa International Hospital
city: Karachi
country: Pakistan
facility: Aga Khan University Hospital MICU
city: Karachi
country: Pakistan
facility: Aga Khan University SICU
city: Karachi
country: Pakistan
facility: Patel Hospital
city: Lahore
country: Pakistan
facility: Doctor's Hospital
city: Lahore
country: Pakistan
facility: National Hospital and Medical Center
city: Nawabshah
country: Pakistan
facility: Peoples Medical College Hospital
city: Peshawar
country: Pakistan
facility: North West General Hospital
city: Batticaloa
country: Sri Lanka
facility: Batticaloa Base Hospital
city: Colombo
country: Sri Lanka
facility: Colombo South Teaching Hospital MICU
city: Colombo
country: Sri Lanka
facility: Colombo South Teaching Hospital SICU
city: Colombo
country: Sri Lanka
facility: Lanka Hospital
city: Colombo
country: Sri Lanka
facility: National Hospital Sri Lanka MICU
city: Colombo
country: Sri Lanka
facility: National Hospital Sri Lanka SICU
city: Colombo
country: Sri Lanka
facility: Sri Jayawardenepura CTICU
city: Colombo
country: Sri Lanka
facility: Sri Jayewardenepura General Hospital GICU
city: Galle
country: Sri Lanka
facility: Karapitiya Teaching Hospital
city: Jaffna
country: Sri Lanka
facility: Jaffna Teaching Hospital
city: Puttalam
country: Sri Lanka
facility: Puttlam Hospital
city: Bangkok
country: Thailand
facility: Chulalongkorn University Hospital
city: Bangkok
country: Thailand
facility: Hospital for Tropical Diseases, Mahidol University
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Bangkok
country: Thailand
facility: Sriraj Hospital
city: Bangkok
country: Thailand
facility: Vajira Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai Hospital Surgical ICU
city: Chiang Mai
country: Thailand
facility: Chiang Mai Medical ICU
city: Chiang Mai
country: Thailand
facility: Nakornping Hospital
city: Hat Yai
country: Thailand
facility: Prince of Songkla University
city: Ongkharak
country: Thailand
facility: Srinakharinwirot University
city: Hanoi
country: Vietnam
facility: National Hospital for Tropical Diseases
city: Ho Chi Minh City
country: Vietnam
facility: Oxford University Clinical Research Unit
Study officials:
affiliation: Department of Intensive Care, Academic Medical Center, University of Amsterdam
name: Marcus J Schultz, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mahidol Oxford Research Unit, University of Oxford
name: Arjen M Dondorp, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Luigi Pisani, MD
role: STUDY_DIRECTOR
affiliation: Hospital Israelita Albert Einstein
name: Ary Serpa Neto, MD, MSc
role: STUDY_CHAIR
References:
citation: Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Esposito 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.
citation: Neto AS, Barbas CSV, Simonis FD, Artigas-Raventos 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, Tschernko EM, Melo MFV, Wrigge H, de Abreu MG, Pelosi P, Schultz MJ; PRoVENT; PROVE Network investigators. Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multicentre, prospective study. Lancet Respir Med. 2016 Nov;4(11):882-893. doi: 10.1016/S2213-2600(16)30305-8. Epub 2016 Oct 4.
citation: Pisani L, Algera AG, Serpa Neto A, Ahsan A, Beane A, Chittawatanarat K, Faiz A, Haniffa R, Hashemian R, Hashmi M, Imad HA, Indraratna K, Iyer S, Kayastha G, Krishna B, Moosa H, Nadjm B, Pattnaik R, Sampath S, Thwaites L, Tun NN, Yunos NM, Grasso S, Paulus F, de Abreu MG, Pelosi P, Dondorp AM, Schultz MJ; PRoVENT-iMIC investigators, MORU and the PROVE network. PRactice of VENTilation in Middle-Income Countries (PRoVENT-iMIC): rationale and protocol for a prospective international multicentre observational study in intensive care units in Asia. BMJ Open. 2018 Apr 28;8(4):e020841. doi: 10.1136/bmjopen-2017-020841.