Clinical trial NCT04978636: Low Tidal Volume Ventilation With Hyperoxia Avoidance During Cardiopulmonary Bypass (The FOCUS Trial)
Official title: The eFfect of cOntinuous Low Tidal Volume Ventilation With Hyperoxia Avoidance During CardiopUlmonary Bypass "FOCUS" Trial Blood Samples
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cardiac Surgery
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: Society of Cardiovascular Anesthesiologists
name: University of Pittsburgh Medical Center
name: Ohio State University
First posted: 2021-07-27
Enrollment: 5502
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: This is a multi-institutional study (CCF, UPMC, OSU) evaluating different ventilation strategies during cardiopulmonary bypass on mortality and postoperative pulmonary complications, with sub-study investigating 8-iso-prostaglandin F2a and sRAGE levels.

Detailed description: The investigators will evaluate the effect of low tidal volume with varying FiO2 fractions during cardiopulmonary bypass on postoperative mortality and pulmonary complications. This will be a prospective, pragmatic, cluster randomized trial including all eligible adult cardiac surgical patients requiring cardiopulmonary bypass. Each week, all operating rooms will be randomized to one of three possible ventilation strategies during the period of cardiopulmonary bypass: 1) continuous low tidal volume ventilation with inspired oxygen fraction at 1.0, 2) continuous low tidal volume ventilation with inspired oxygen fraction at 0.21, and 3) no ventilation (apnea). The investigators will anticipate increase in plasma sRAGE and 8-iso-prostaglandin F2a levels in all three groups of patients during CPB with the highest levels immediately after cross-clamp release. The investigators will anticipate significant difference with at least 25% lower sRAGE levels in this group. The sub-study will also provide preliminary data on the behavior of the 8-iso-prostaglandin F2a which will be useful in further investigation of other targeted interventions to reduce ischemia-reperfusion injury to the lung during routine cardiac surgical operations.

Eligibility criteria: Inclusion Criteria:

* \>18 years of age
* Male and female patients undergoing elective cardiac surgeries requiring cardiopulmonary bypass.

Exclusion Criteria:

Emergency surgeries, surgeries requiring lung isolation and one-lung ventilation (OLV), heart or lung transplants, and mechanical circulatory support device implantation pulmonary thrombendarterectomies.

* Surgeries requiring one-lung ventilation will be excluded because of the inability to employ study intervention and the differential treatment of the lungs likely confounding any potential effect from the planned intervention.
* Lung transplant surgeries will be excluded for similar reasons as well as other confounding effects affecting the primary composite outcome.
* Heart transplants and mechanical circulatory support device implantation surgeries will be excluded because these patients already receive intervention as part of the institutional protocol at the primary study site.

Primary outcomes:
measure: Occurrence of Composite including STS 30 day Mortality and postoperative pulmonary complications
timeFrame: Within 30 days of surgery
Secondary outcomes:
measure: CPB time
timeFrame: During surgery
measure: ICU LOS
timeFrame: Within 30 days of surgery
measure: Early respiratory failure - PaO2/FiO2 ratio < 200 mmHg at any time within the first 24 hours of ICU admission
timeFrame: 24 hours
measure: Hospital LOS
timeFrame: Within 30 days of surgery
measure: Reintubation
timeFrame: Within 30 days of surgery
measure: Need for tracheostomy
timeFrame: Within 30 days of surgery
measure: Pleural effusion requiring drainage
timeFrame: Within 30 days of surgery
measure: Pneumonia
timeFrame: Within 30 days of surgery
measure: Readmission
timeFrame: within 30 days of surgery
measure: 30-day mortality
timeFrame: Within 30 days of surgery
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Marta Kelava, MD
role: PRINCIPAL_INVESTIGATOR
References: