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

NCT ID: NCT00512265

Last Updated: 2013-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2009-01-31

Brief 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.

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).

Conditions

Pulmonary Morbidity

Keywords

n-acetylcysteine; esophagectomy; inflammatory reaction; pulmonary morbidity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

n-acetylcysteine

Intervention Type: DRUG

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

2

placebo (250mL glucose 5%) at time of induction of anaesthesia placebo (250mL glucose 5%) on post-op days 1-3

Group Type: PLACEBO_COMPARATOR

250mL glucose 5%

Intervention Type: DRUG

placebo (250mL glucose 5%) at time of induction of anaesthesia placebo (250mL glucose 5%) on post-op days 1-3

Interventions

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

Intervention Type: DRUG

250mL glucose 5%

placebo (250mL glucose 5%) at time of induction of anaesthesia placebo (250mL glucose 5%) on post-op days 1-3

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Triemli Hospital

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Urs Zingg, PD, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Basel, Switzerland, Dep. Surgery

Andreas Zollinger, MD

Role: STUDY_DIRECTOR

Departement of Anaesthesia and Intensive Care,Triemli Hospital, Zurich, Switzerland

Locations

University Hospital Basel

Basel, , Switzerland

Department of Surgery, Triemli Hospital, Zurich, Switzerland

Zurich, , Switzerland

Countries

Switzerland

Other Identifiers

2005DR4333

Identifier Type: -

Identifier Source: org_study_id