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

This study has been completed.
Sponsor:
Collaborator:
Triemli Hospital
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT00512265
First received: August 6, 2007
Last updated: August 27, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Pulmonary Morbidity
Drug: n-acetylcysteine
Drug: 250mL glucose 5%
Phase 4

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

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Influence of NAC on peri- and postoperative oxygenation parameters pO2, pO2/FiO2 oxygenation index), pCO2, HCO3-, Base Excess, pH. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Influence of NAC on postoperative morbidity and mortality. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Long term analysis of quality of life after esophagectomy. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Influence of NAC on peri- and postoperative oxygenation parameters pO2, pO2/FiO2 (oxygenation index), pCO2, HCO3-, Base Excess, pH. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Compare inflammatory reaction left vs right lung and other compartments [ Time Frame: 2 years from launch ] [ Designated as safety issue: No ]

Enrollment: 29
Study Start Date: January 2006
Study Completion Date: January 2009
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
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
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
Placebo Comparator: 2
placebo (250mL glucose 5%) at time of induction of anaesthesia placebo (250mL glucose 5%) on post-op days 1-3
Drug: 250mL glucose 5%
placebo (250mL glucose 5%) at time of induction of anaesthesia placebo (250mL glucose 5%) on post-op days 1-3

Detailed 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).

  Eligibility

Ages Eligible for Study:   20 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00512265

Locations
Switzerland
University Hospital Basel
Basel, Switzerland
Department of Surgery, Triemli Hospital, Zurich, Switzerland
Zurich, Switzerland
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Triemli Hospital
Investigators
Principal Investigator: Urs Zingg, PD, MD University Hospital Basel, Switzerland, Dep. Surgery
Study Director: Andreas Zollinger, MD Departement of Anaesthesia and Intensive Care,Triemli Hospital, Zurich, Switzerland
  More Information

No publications provided

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT00512265     History of Changes
Other Study ID Numbers: 2005DR4333
Study First Received: August 6, 2007
Last Updated: August 27, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Basel, Switzerland:
n-acetylcysteine
esophagectomy
inflammatory reaction
pulmonary morbidity

Additional relevant MeSH terms:
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on April 22, 2014