N-Acetylcysteine vs Placebo as Adjunctive Treatment in Pediatric Leukemia

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical trial is to analyze the effect of N-Acetylcysteine administration towards blood oxidant level, transaminase enzyme, and bilirubin level in ALL children who undergo induction phase of chemotherapy. The main question it aims to answer is whether N-Acetylcysteine can decrease oxidative stress level and reduce hepatotoxicity complication. Participants will be evaluated for MDA level, transaminase enzymes and bilirubin level before, during, and after the chemotherapy. Participants will be given capsules containing 600mg of N-Acetylcysteine as adjunctive treatment during the 6 weeks induction phase of chemotherapy. Researchers will compare the lab results to the placebo group to see if there is any significant difference in the results.

Detailed Description
-----------------
The current study has been designed as a randomized single-blind placebo-controlled clinical trial. Sample size calculation for the study was 18 newly diagnosed ALL children in each group using the numerical unpaired two groups data analysis formula. Subjects were recruited from newly diagnosed children with ALL and will start the induction phase of chemotherapy both in hospital ward and outpatient clinic in the Child Health Department at Cipto Mangunkusumo Hospital from August to December 2020. Subjects' parents received an explanation about the study, including the objective and benefits of the study, and also the procedure which will be held. Parents were then asked about the willingness to join the study and signed the form. Subjects were randomized consecutively and distributed into two groups. Randomization was done by a third person to decide the distribution of the subjects based on the serial number of randomization. Subjects in treatment group will be given capsules containing 600 mg of NAC and subjects in the control group will be given capsules containing placebo (lactose) as the adjunctive treatment during the 6 week induction phase of chemotherapy. Both of the medicines were prepared by the Installation of Pharmacy in Cipto Mangunkusumo National Hospital with the same type and same color of capsules. NAC will be administered during the induction phase of chemotherapy starting in the first week until 6 weeks. This study will analyze change of MDA levels, transaminase enzyme levels, and bilirubin levels before and after the 6th week of the induction phase of chemotherapy.

Official Title
-----------------
N-Acetylcysteine vs Placebo as Adjunctive Treatment in Pediatric Leukemia: A Single Blind, Randomized Controlled Trial

Conditions
-----------------
Lymphoblastic Leukemia, Acute, Childhood

Intervention / Treatment
-----------------
* Drug: N-Acetylcysteine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: newly diagnosed ALL-Standard Risk children who will undergo the induction phase of chemotherapy from 1st week until 6th week parents agreed to participate in the study and signed the informed consent Exclusion Criteria: subjects with allergy or contraindicated to consuming N-acetylcysteine subjects with liver dysfunction based on clinical and laboratory tests diagnosed before joining the study subjects who already consume other antioxidants (vitamin A, vitamin C, and vitamin E).

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 10 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects were randomized consecutively and distributed into two groups. Randomization was done by a third person to decide the distribution of the subjects based on the serial number of randomization.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NAC Group<br>Participants of this group was given capsules containing 600mg N-acetylcysteine | Drug: N-Acetylcysteine<br>* Subjects in treatment group will be given capsules containing 600 mg of NAC<br>* Other names: Fluimucil;|
| Placebo Comparator: Placebo<br>Participants of this group was given capsules containing lactose | Drug: Placebo<br>* subjects in the control group will be given capsules containing placebo (lactose)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MDA (Malondialdehyde) | nanomol | Change from Baseline Malondialdehyde level at 7 week | 
| Aspartate aminotransferase | u/L | Change from Baseline Aspartate aminotransferase level at 7 week | 
| Alanine transaminase | u/L | Change from Baseline Alanine transaminase level at 7 week | 
| Bilirubin | mg/dL | Change from Baseline Bilirubin level at 7 week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Malondialdehyde, N-acetylcysteine, Oxidative stress