Pulmonary Morbidity Clinical Trial
Official title:
Influence of N-Acetylcysteine on Morbidity, Oxygenation and Cytokine Levels in Partial or Total Esophagectomy for Cancer. A Multicenter, Prospective, Randomised Double Blind, Placebo-controlled Study
The purpose of this study is to evaluate the effect of high-dose n-acetylcysteine on inflammatory reaction, pulmonary morbidity, oxygenation and quality of life in patients undergoing transthoracic, partial or total resection of the esophagus for cancer.
Cancer of the esophagus has a poor long term prognosis as well as high perioperative
morbidity. Pulmonary complications play thereby a major role. The standard procedure is
either a combined transabdominal/transthoracic approach, which allows better visualisation
of the tumor and more radical surgery (which may increase R0 resections and consequently
overall survival) or a blunt transhiatal technique. In Zurich, Basel and Lucerne, the
combined technique is the standard procedure. The combined surgical approach, pre-existing
pulmonary disorders, poor nutritional status and the release of pro-inflammatory cytokines
may be important contributing factors to pulmonary complications such as pneumonia,
atelectasis, pleural effusions and the Acute Respiratory Distress Syndrome (ARDS).
N-Acetylcysteine (NAC) has been shown to have direct and indirect oxygen scavenging
abilities. In severe sepsis and acute respiratory distress syndrome, positive effects of NAC
on morbidity and mortality were discovered. Aim of this study is to assess the influence of
NAC on morbidity, oxygenation parameters and cytokine levels.
According to power analysis, 90 patients have to be included in the trial. A multicenter
approach was chosen to finish the study within 3 years. Respective to the average number of
operations per institution and year, the following distribution is planned: Triemli Hospital
40, University Hospital Basel 30, Kantonsspital Lucerne 20. Inclusion criteria for this
trial are patients undergoing thoraco-abdomino-cervical or abdomino-thoracic esophagectomy
for cancer between 20 and 90 years and given informed consent. Exclusion criteria are known
allergy or hypersensitivity to NAC and pregnancy. Patients are randomised to receive either
high dose N-Acetylcysteine administered perioperatively and postoperatively for three days
(150mg/kg perioperatively and 50mg/kg days 1-3) or placebo (glucose 5%).
Pre-, peri- and postoperatively cytokines (IL-1, IL-1ra, IL-6, IL-8, IL-10, TNF-α), are
quantified by enzyme-linked immuno assay (ELISA) from blood, broncho-alveolar lavage and
lavage of pleural space. Leucocytes, C-reactive protein, Procalcitonin and oxygenation
parameters (arterial blood gas analyses = ABGA) are regularly measured. Morbidity and
mortality is assessed. Furthermore, all patients are asked to complete a quality of life
questionnaire (EORTC QLQ-OES18 and 30, SF-36) before and after the operation (12, 24, 36
months post-op).
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment