Practice of Ventilation in Middle-Income Countries (PRoVENT-iMIC)

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

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.

Study Overview

• Status: Completed
• Conditions: Respiratory Distress Syndrome, Adult; Acute Respiratory Failure; Mechanical Ventilation

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.

• Study Type: Observational
• Enrollment (Actual): 1315

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

consecutive intubated and ventilated intensive care unit patients

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Mechanical Ventilation; Patients under mechanical ventilation in the ICU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tidal volume size	Tidal volume size in milliliters per kilogram of predicted body weight	Day 1 to Day 3 from initiation of mechanical ventilation
Positive end-expiratory pressure	Pressure in cm of water	Day 1 to Day 3 from initiation of mechanical ventilation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients at risk of ARDS	Risk of ARDS is stratified using the Lung Injury Prediction Score.	On the date of inclusion
Inspired Oxygen Concentration	expressed as fraction of inspired oxygen	Day 1 to Day 3 from initiation of mechanical ventilation
Plateau pressure	Pressure in cm of water	Day 1 to Day 3 from initiation of mechanical ventilation
Peak pressure	Peak away pressure in cm of water	Day 1 to Day 3 from initiation of mechanical ventilation
Driving pressure	pressure in cm of water	Day 1 to Day 3 from initiation of mechanical ventilation
Respiratory Rate	in breaths per minute	Day 1 to Day 3 from initiation of mechanical ventilation
Minute Volume	expressed as liters per minute	Day 1 to Day 3 from initiation of mechanical ventilation
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
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
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
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
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
Length of stay in ICU	Time between admission and discharge or death	Until day 35 from study initiation
All-cause ICU mortality	Any death during ICU stay	Until day 35 from study initiation
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

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Hospital Israelita Albert Einstein; Mahidol Oxford Tropical Medicine Research Unit
• Investigators: Principal Investigator: Marcus J Schultz, MD, PhD, Department of Intensive Care, Academic Medical Center, University of Amsterdam; Principal Investigator: Arjen M Dondorp, MD, PhD, Mahidol Oxford Research Unit, University of Oxford; Study Director: Luigi Pisani, MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Study Chair: Ary Serpa Neto, MD, MSc, Hospital Israelita Albert Einstein

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• Study website
• Protective Ventilation Network website

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): November 29, 2018
• Study Completion (Actual): January 29, 2019

Study Registration Dates

• First Submitted: June 12, 2017
• First Submitted That Met QC Criteria: June 14, 2017
• First Posted (Actual): June 15, 2017

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 2, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Middle-income countries
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Insufficiency; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: PRoVENT-iMIC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No