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NCT02918877: APLICS

Anesthetics to Prevent Lung Injury in Cardiac Surgery

Completed Phase 1, PHASE2 Results posted Last updated 5 May 2021
What this trial tests

Phase 1, PHASE2 trial testing Sevoflurane in Inflammatory Lung Injury in 51 participants. Completed in 1 February 2021.

Timeline
9 June 2017
Primary endpoint
24 December 2018
1 February 2021

Quick facts

Lead sponsorBeth Israel Deaconess Medical Center
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingsingle
Primary purposeprevention
Enrollment51
Start date9 June 2017
Primary completion24 December 2018
Estimated completion1 February 2021
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Beth Israel Deaconess Medical Center

Who can join

18 and older, any sex, with Inflammatory Lung Injury or Ischemia-Reperfusion Lung Injury. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Bronchoalveolar Lavage (BAL) Concentration of TNF Alpha (pg/mL) Primary · Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass

Inflammatory mediator found in BAL fluid during lung inflammation

Pre-Bypass
GroupValue95% CI
Inhaled Anesthesia0.530.53 – 4.99
Intravenous Anesthesia0.530.53 – 13.80
Post-Bypass
GroupValue95% CI
Inhaled Anesthesia22.061.75 – 623.08
Intravenous Anesthesia102.042.21 – 408.05
Difference
GroupValue95% CI
Inhaled Anesthesia17.241.22 – 536.77
Intravenous Anesthesia101.511.47 – 402.84
Number of Patients With Postoperative Pulmonary Complications Secondary · Assessed daily, beginning on the first day after surgery, until hospital discharge or death. On average at our institution, most patients are discharged within 7 days so this is the expected time frame for follow up.

Composite endpoint of clinically relevant pulmonary complications

Prolonged intubation (greater than 48hrs)
GroupValue95% CI
Inhaled Anesthesia0
Intravenous Anesthesia3
Failed extubation (re-intubated within 24hrs)
GroupValue95% CI
Inhaled Anesthesia0
Intravenous Anesthesia1
Reintubation (greater than 24hrs after extubation)
GroupValue95% CI
Inhaled Anesthesia0
Intravenous Anesthesia2
Pulmonary edema
GroupValue95% CI
Inhaled Anesthesia4
Intravenous Anesthesia8
Pleural effusion
GroupValue95% CI
Inhaled Anesthesia17
Intravenous Anesthesia21
Atelectasis
GroupValue95% CI
Inhaled Anesthesia16
Intravenous Anesthesia19
Infiltrate/consolidation
GroupValue95% CI
Inhaled Anesthesia6
Intravenous Anesthesia6
Pneumothorax
GroupValue95% CI
Inhaled Anesthesia1
Intravenous Anesthesia5
BAL Concentration of IL1b (pg/mL) Secondary · Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass

Inflammatory mediator found in BAL fluid during lung inflammation

Pre-Bypass
GroupValue95% CI
Inhaled Anesthesia0.420.06 – 2.61
Intravenous Anesthesia0.870.28 – 2.54
Post-Bypass
GroupValue95% CI
Inhaled Anesthesia8.560.21 – 64.77
Intravenous Anesthesia14.371.88 – 76.10
Difference
GroupValue95% CI
Inhaled Anesthesia8.30-0.67 – 59.64
Intravenous Anesthesia11.001.18 – 66.14
BAL Concentration of IL6 (pg/mL) Secondary · Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass

Inflammatory mediator found in BAL fluid during lung inflammation

Pre-Bypass
GroupValue95% CI
Inhaled Anesthesia30.706.77 – 96.60
Intravenous Anesthesia31.355.27 – 165.93
Post-Bypass
GroupValue95% CI
Inhaled Anesthesia275.196.21 – 1134.33
Intravenous Anesthesia297.3540.59 – 1277.04
Difference
GroupValue95% CI
Inhaled Anesthesia220.68-12.41 – 1046.00
Intravenous Anesthesia259.3230.33 – 1039.58
BAL Concentration of IL8 (pg/mL) Secondary · Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass

Inflammatory mediator found in BAL fluid during lung inflammation

Pre-Bypass
GroupValue95% CI
Inhaled Anesthesia2008.50341.25 – 16444.75
Intravenous Anesthesia6528.50625.00 – 16332.25
Post-Bypass
GroupValue95% CI
Inhaled Anesthesia8019.50998.25 – 100438.00
Intravenous Anesthesia27789.504780.50 – 154087.75
Difference
GroupValue95% CI
Inhaled Anesthesia4701.00-290.25 – 77061.00
Intravenous Anesthesia16230.001399.25 – 123098.50
BAL Concentration of MCP1 (pg/mL) Secondary · Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass

Inflammatory mediator found in BAL fluid during lung inflammation

Pre-Bypass
GroupValue95% CI
Inhaled Anesthesia509.50249.25 – 1415.75
Intravenous Anesthesia977.50336.50 – 1225.75
Post-Bypass
GroupValue95% CI
Inhaled Anesthesia496.00184.25 – 2153.25
Intravenous Anesthesia883.50651.50 – 4380.50
Difference
GroupValue95% CI
Inhaled Anesthesia148.00-265.75 – 869.75
Intravenous Anesthesia479.50-104.25 – 1482.75
BAL Concentration of sRAGE (pg/mL) Secondary · Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass

Biomarker of lung injury (RAGE - receptor for advance glycosylation end products)

Pre-Bypass
GroupValue95% CI
Inhaled Anesthesia156.5044.00 – 383.00
Intravenous Anesthesia16460.75 – 380.50
Post-Bypass
GroupValue95% CI
Inhaled Anesthesia597.00220.50 – 1195.00
Intravenous Anesthesia465.00206.00 – 2120.50
Difference
GroupValue95% CI
Inhaled Anesthesia402.50155.25 – 1063.25
Intravenous Anesthesia224.50-69.25 – 2088.25

Adverse events — posted to ClinicalTrials.gov

Time frame: During hospital length of stay ~7 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Inhaled Anesthesia
Serious: 0/18 (0%)
Deaths: 0/18
Intravenous Anesthesia
Serious: 0/22 (0%)
Deaths: 1/22
Other adverse events (12 terms — click to expand)

ReactionSystemInhaled AnesthesiaIntravenous Anesthesia
Pleural effusionRespiratory, thoracic and mediastinal disorders
AtelectasisRespiratory, thoracic and mediastinal disorders
Hypoxia (PaO2/FiO2 < 300)Respiratory, thoracic and mediastinal disorders
Respiratory acidosis (PaCO2 > 45)Respiratory, thoracic and mediastinal disorders
Pulmonary edemaRespiratory, thoracic and mediastinal disorders
Infiltrate/consolidationRespiratory, thoracic and mediastinal disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Prolonged intubation (greater than 48hrs)Respiratory, thoracic and mediastinal disorders
Reintubation (greater than 24hrs after extubation)Respiratory, thoracic and mediastinal disorders
Failed extubation (re-intubated within 24hrs)Respiratory, thoracic and mediastinal disorders
PneumoniaRespiratory, thoracic and mediastinal disorders
BrochospasmRespiratory, thoracic and mediastinal disorders

Data from ClinicalTrials.gov NCT02918877 adverse events section.

Sponsor's own description

The purpose of this study is to investigate whether the use of inhaled anesthetics, compared to intravenous anesthetics, can affect the amount of lung inflammation and postoperative respiratory complications seen after cardiac surgery.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Anesthetics to Prevent Lung Injury in Cardiac Surgery (APLICS): a protocol for a randomized controlled trial.
    O'Gara B, Subramaniam B, Shaefi S, Mueller A, et al · · 2019 · cited 7× · PMID 31151474 · DOI 10.1186/s13063-019-3400-x
  2. Anesthetics to Prevent Lung Injury in Cardiac Surgery: A Randomized Controlled Trial.
    O'Gara BP, Shaefi S, Gasangwa DV, Patxot M, et al · · 2022 · cited 2× · PMID 35798633 · DOI 10.1053/j.jvca.2022.04.018
  3. Anesthetics to Prevent Lung Injury in Cardiac Surgery (APLICS): A protocol for a randomized, controlled trial
    O'Gara B, Subramaniam B, Shaefi S, Mueller A, et al · · 2019 · DOI 10.21203/rs.2.28/v3

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