Safety and Efficacy of Adding Intravenous N-acetyl Cysteine in Colon Surgeries

Safety and Efficacy of Adding Intravenous N-acetyl Cysteine to Parenteral L-alanyl L-glutamine in Hospitalized Patients Undergoing Colon Surgeries

The use of antioxidant agents in the prevention or decreasing the severity of postoperative systemic inflammatory response syndrome after colonic surgeries adopted nowadays. Therefore, it is of interest to investigate safety and efficacy of administrating short term intravenous (IV) N acetyl cysteine as add on to l alany l glutamine and total parenteral nutrition on the marker of oxidative stress malondialdehyde and anti- inflammatory marker tumor necrosis factor alpha in patients undergoing colonic surgeries through a prospective, randomized, double blinded, controlled clinical trial

Study Overview

• Status: Completed
• Conditions: Systemic Inflammatory Response Syndrome
• Intervention / Treatment: Drug: N Acetyl L Cysteine; Other: dextrose 5%

Detailed Description

A prospective, randomized, double blinded, controlled clinical trial will be carried out on 60 patients, who will admit to the critical care unit, Ain Shams hospitals, Cairo, Egypt, following colon surgeries. Before the start of the study, eligible patients were randomized using computer generated list in order to allocate participants to either Group I (n acetyl cysteine group) or Group II (control group) in an equal manner No medication will take before the surgery and only oral fluids were allowed on the day before the operation. All eligible patients underwent bowel preparation with oral 1.745 g/ 30 ml magnesium citrate, and phosphate containing enema on the day before surgery. All patients received the general anesthesia with endotracheal intubation and muscle relaxant.

Data management and analysis were performed using the Statistical Package for Social Sciences (SPSS) software for Windows version 18

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• need for ICU admission after colonic surgery
• requirement of total parenteral nutrition for at least 5 days due to failure of or contraindication for enteral nutrition
• signing a written informed consent.

Exclusion Criteria:

• patients with persistent hemodynamic instability (systolic blood pressure <80 mm Hg), renal impairment, hepatic insufficiency, severe or uncontrolled sepsis, persistent metabolic acidosis, head trauma,and heart failure
• any sensitivity to components of L-alanyl L-glutamine (Dipeptiven®, Fresenius Kabi, Germany) or N acetyl cysteine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: N acetylcysteine group; N Acetyl L Cysteine IV bolus (100 mg/kg dissolved in dextrose5%) infused over 15 minutes, followed by continuous infusion of 50mg/kg/day dissolved in dextrose 5% starting 1hr before induction of anesthesia, and continued for 48 hours after operation	Drug: N Acetyl L Cysteine; 100 mg/kg n acetyl cysteine dissolved in dextrose5%
Placebo Comparator: placebo group; received equal volume of dextrose 5% administrated at the same rate and duration as in the study group as a placebo	Other: dextrose 5%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
assessing a change in the level of tumor necrosis factor alpha (TNF alpha) as ant-inflammatory marker reflecting n acetyl cysteine efficacy	TNF alpha was measured using ELISA technique	Venous blood samples were obtained before surgery (baseline evaluation), and on day two after surgery for measuring changes in TNF ALPHA
assessing a change in the level of malondialdehyde as antioxidant marker in the venous blood sample reflecting n acetyl cysteine efficacy	malondialdehyde was measured using colorimetric method for assay	Venous blood samples were obtained before surgery (baseline evaluation), and on day two after surgery for measuring changes in malondialdehyde level

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
measuring safety of N acetyl cysteine (adverse effects)	recording any adverse effects that may appear	from the beginning of the study till the patient is discharged from the hospital(up to one week)

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Study Director: manal elhammsy, prof, Ain Shams University , faculty of pharmacy

Publications and helpful links

General Publications

• Hamamsy ME, Bondok R, Shaheen S, Eladly GH. Safety and efficacy of adding intravenous N-acetylcysteine to parenteral L-alanyl-L-glutamine in hospitalized patients undergoing surgery of the colon: a randomized controlled trial. Ann Saudi Med. 2019 Jul-Aug;39(4):251-257. doi: 10.5144/0256-4947.2019.251. Epub 2019 Aug 5.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2015
• Primary Completion (Actual): October 15, 2016
• Study Completion (Actual): October 15, 2016

Study Registration Dates

• First Submitted: June 15, 2018
• First Submitted That Met QC Criteria: July 17, 2018
• First Posted (Actual): July 18, 2018

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Shock; Systemic Inflammatory Response Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: 79

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All the individual participant data will be stored on the computer and will be available on request only
• IPD Sharing Time Frame: it will be available once the trial ends, and for 3 months after publication
• IPD Sharing Access Criteria: data will be available on request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No