Influence of N-Acetylcysteine on Morbidity, Oxygenation and Cytokine Levels in Partial or Total Esophagectomy for Cancer

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00512265
• Other study ID #: 2005DR4333
• Status: Completed
• Phase: Phase 4
• First received: August 6, 2007
• Last updated: August 27, 2013
• Start date: January 2006
• Est. completion date: January 2009

Study information

• Verified date: August 2013
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: January 2009
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 90 Years

Eligibility

Inclusion Criteria:

• elective, abdomino-thoracic esophagectomy

• elective, thoraco-abdomino-cervical esophagectomy

• age 20-90 years

• informed consent given

Exclusion Criteria:

• emergency procedures

• patients with increased bronchorrhoea

• hypersensitivity against n-acetylcysteine

• pregnancy

• lactation

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pulmonary Morbidity

Intervention

Drug:
• n-acetylcysteine
150mg/kg N-Acetylcysteine in 250mL Glucose 5% at time of induction of anaesthesia 50mg/kg N-Acetylcysteine in 250mL Glucose 5% on post-op days 1-3
• 250mL glucose 5%
placebo (250mL glucose 5%) at time of induction of anaesthesia placebo (250mL glucose 5%) on post-op days 1-3

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel
Switzerland	Department of Surgery, Triemli Hospital, Zurich, Switzerland	Zurich

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Triemli Hospital

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Influence of n-acetylcysteine on inflammatory reaction measured by 1. cytokines in blood, broncho-alveolar lavage and pleural lavage; 2. postoperative course of Leucocytes, C - reactive protein and Procalcitonin.		1 year	No
Secondary	Influence of NAC on peri- and postoperative oxygenation parameters pO2, pO2/FiO2 oxygenation index), pCO2, HCO3-, Base Excess, pH.		1 year	No
Secondary	Influence of NAC on postoperative morbidity and mortality.		1 year	No
Secondary	Long term analysis of quality of life after esophagectomy.		5 years	No
Secondary	Influence of NAC on peri- and postoperative oxygenation parameters pO2, pO2/FiO2 (oxygenation index), pCO2, HCO3-, Base Excess, pH.		1 year	No
Secondary	Compare inflammatory reaction left vs right lung and other compartments		2 years from launch	No