Re-Evaluation of the Effects of High PEEP During General Anesthesia For Surgery (REPEAT) (REPEAT)

Re-Evaluation of the Effects of High PEEP During General Anesthesia For Surgery - An Individual Patient Data Meta-Analysis of PROVHILO, iPROVE and PROBESE

Aiming to understand the isolated impact of high PEEP in patients undergoing mechanical ventilation for general anesthesia for surgery, three appropriately sized international multicentre randomized controlled trials have been performed over recent years: the 'PROtective Ventilation using HIgh versus LOw PEEP trial (PROVHILO), the 'individualized PeRioperative Open-lung Ventilation trial' (iPROVE), and the 'Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients trial' (PROBESE). These three trials had several similarities in key areas of their study protocols, inclusion and exclusion criteria, and collected data, and even the primary and secondary outcomes. Of note, the three trials combined high PEEP with recruitment manoeuvres. This allows an individual patient data meta-analysis.

Study Overview

• Status: Completed
• Conditions: Surgery; Mechanical Ventilation Complication; Pulmonary Complication
• Intervention / Treatment: Behavioral: High PEEP; Behavioral: Low PEEP

• Study Type: Observational
• Enrollment (Actual): 3837

Contacts and Locations

Study Locations

• Germany
  • Dresden, Germany
    • University Hospital Carl Gustav Carus, Technische Universität Dresden
• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam UMC, University of Amsterdam
• Spain
  • Valencia, Spain
    • Hospital Clinico Universitario de Valencia

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adult patients undergoing mechanical ventilation for general anesthesia for surgery.

Description

Inclusion Criteria:

- Enrolled into one of the three studies (PROVHILO, iPROVE or PROBESE) to either high PEEP or low PEEP

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
High PEEP; Use of high levels of PEEP with recruitment maneuvers	Behavioral: High PEEP; Use of high levels of PEEP combined with recruitment maneuvers and low tidal volume ventilation during general anesthesia
Low PEEP; Use of low levels of PEEP without recruitment maneuvers	Behavioral: Low PEEP; Use of low levels of PEEP without recruitment maneuvers and low tidal volume ventilation during general anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of postoperative pulmonary complications	Collapsed composite of complications developing within the first seven postoperative days, including: Mild respiratory failure; or Severe respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or Pulmonary infection; or Pleural effusion; or Atelectasis; or Pneumothorax; or Bronchospasm.	Until day seven or hospital discharge, whichever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of intensive care unit admission	Incidence of intensive care unit admission during hospital stay	Until hospital discharge, death or 100 days, whichever comes first
Incidence of severe postoperative pulmonary complications	Collapsed composite of complications developing within the first seven postoperative days, including: Severe respiratory failure; or Acute Respiratory Distress Syndrome (ARDS); or Pulmonary infection; or Pleural effusion; or Atelectasis; or Pneumothorax; or Bronchospasm	Until day seven or hospital discharge, whichever comes first
Incidence of extrapulmonary pulmonary complications	Collapsed composite of complications developing within the first seven postoperative days, including: Systemic Response Inflammatory Syndrome; or Sepsis; or Septic Shock; or Acute Kidney Injury.	Until day seven or hospital discharge, whichever comes first
Incidence of intraoperative complications	Defined as intraoperative hypotension; or need for rescue for desaturations; or need for vasoactive drugs.	Intraoperatively
Hospital length of stay	Duration of hospital length of stay in days	Until hospital discharge, death or 100 days, whichever comes first
Incidence of 7-day mortality	Mortality during the first seven days of hospitalization	Until day seven or hospital discharge, whichever comes first
Incidence of in-hospital mortality	Mortality during hospitalization	Until hospital discharge, death or 100 days, whichever comes first
Incidence of major postoperative complications	Collapsed composite of complications developing within the first seven postoperative combining severe postoperative pulmonary complications, sepsis, septic shock and/or acute kidney injury)	Until day seven or hospital discharge, whichever comes first

Collaborators and Investigators

• Sponsor: Hospital Israelita Albert Einstein
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); University Hospital Carl Gustav Carus; Hospital Clínico Universitario de Valencia

Publications and helpful links

General Publications

• Ferrando C, Soro M, Canet J, Unzueta MC, Suarez F, Librero J, Peiro S, Llombart A, Delgado C, Leon I, Rovira L, Ramasco F, Granell M, Aldecoa C, Diaz O, Balust J, Garutti I, de la Matta M, Pensado A, Gonzalez R, Duran ME, Gallego L, Del Valle SG, Redondo FJ, Diaz P, Pestana D, Rodriguez A, Aguirre J, Garcia JM, Garcia J, Espinosa E, Charco P, Navarro J, Rodriguez C, Tusman G, Belda FJ; iPROVE investigators (Appendices 1 and 2). Rationale and study design for an individualized perioperative open lung ventilatory strategy (iPROVE): study protocol for a randomized controlled trial. Trials. 2015 Apr 27;16:193. doi: 10.1186/s13063-015-0694-1.
• Ferrando C, Soro M, Unzueta C, Suarez-Sipmann F, Canet J, Librero J, Pozo N, Peiro S, Llombart A, Leon I, India I, Aldecoa C, Diaz-Cambronero O, Pestana D, Redondo FJ, Garutti I, Balust J, Garcia JI, Ibanez M, Granell M, Rodriguez A, Gallego L, de la Matta M, Gonzalez R, Brunelli A, Garcia J, Rovira L, Barrios F, Torres V, Hernandez S, Gracia E, Gine M, Garcia M, Garcia N, Miguel L, Sanchez S, Pineiro P, Pujol R, Garcia-Del-Valle S, Valdivia J, Hernandez MJ, Padron O, Colas A, Puig J, Azparren G, Tusman G, Villar J, Belda J; Individualized PeRioperative Open-lung VEntilation (iPROVE) Network. Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial. Lancet Respir Med. 2018 Mar;6(3):193-203. doi: 10.1016/S2213-2600(18)30024-9. Epub 2018 Jan 19.
• Bluth T, Teichmann R, Kiss T, Bobek I, Canet J, Cinnella G, De Baerdemaeker L, Gregoretti C, Hedenstierna G, Hemmes SN, Hiesmayr M, Hollmann MW, Jaber S, Laffey JG, Licker MJ, Markstaller K, Matot I, Muller G, Mills GH, Mulier JP, Putensen C, Rossaint R, Schmitt J, Senturk M, Serpa Neto A, Severgnini P, Sprung J, Vidal Melo MF, Wrigge H, Schultz MJ, Pelosi P, Gama de Abreu M; PROBESE investigators; PROtective VEntilation Network (PROVEnet); Clinical Trial Network of the European Society of Anaesthesiology (ESA). Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial. Trials. 2017 Apr 28;18(1):202. doi: 10.1186/s13063-017-1929-0. Erratum In: Trials. 2017 Jun 1;18(1):247.
• PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology; Hemmes SN, Gama de Abreu M, Pelosi P, Schultz MJ. High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet. 2014 Aug 9;384(9942):495-503. doi: 10.1016/S0140-6736(14)60416-5. Epub 2014 Jun 2.
• Hemmes SN, Severgnini P, Jaber S, Canet J, Wrigge H, Hiesmayr M, Tschernko EM, Hollmann MW, Binnekade JM, Hedenstierna G, Putensen C, de Abreu MG, Pelosi P, Schultz MJ. Rationale and study design of PROVHILO - a worldwide multicenter randomized controlled trial on protective ventilation during general anesthesia for open abdominal surgery. Trials. 2011 May 6;12:111. doi: 10.1186/1745-6215-12-111.
• Campos NS, Bluth T, Hemmes SNT, Librero J, Pozo N, Ferrando C, Ball L, Mazzinari G, Pelosi P, Gama de Abreu M, Schultz MJ, Serpa Neto A; REPEAT; investigators for the PROVHILO study; iPROVE study; PROBESE study investigators; PROVE Network. Intraoperative positive end-expiratory pressure and postoperative pulmonary complications: a patient-level meta-analysis of three randomised clinical trials. Br J Anaesth. 2022 Jun;128(6):1040-1051. doi: 10.1016/j.bja.2022.02.039. Epub 2022 Apr 15.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): January 30, 2020

Study Registration Dates

• First Submitted: May 2, 2019
• First Submitted That Met QC Criteria: May 2, 2019
• First Posted (Actual): May 3, 2019

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Surgery; Postoperative pulmonary complications; Mechanical ventilation; PEEP; Individual patient data meta-analysis
• Other Study ID Numbers: REPEAT (Company Internal)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The harmonized dataset will be available after the publication of the main results and under request to the steering committee
• IPD Sharing Time Frame: After the publication of the main results
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

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