N-Acetylcysteine Role on Urinary KIM-1 and Serum Creatinine Level in Cancer Patient With Cisplatin Based Chemotherapy
Phase: PHASE2
Conditions: Kidney Function Issue, Acute Kidney Injury, Cancer (Solid Tumors), Kidney Function Tests, Acetylcysteine Adverse Reaction
Sponsor: Fakultas Kedokteran Universitas Indonesia

Study Protocol and Statistical Analysis Plan 
Title of Study: N-Acetylcysteine Roles in Preserving Renal Function Measured by Urinary 
KIM-1 (Kidney Injury Molecule-1) and Serum Creatinine on Cancer Patients 
With Cisplatin Based Chemotherapy: A Randomized Placebo-Controlled Trial 
ClinicalTrial.gov Identifier: NCT07156786 
Principal Investigator: Oryza Gryagus Prabu, MD  
Date of Document: 12/09/2025
 

Table of Contents 
Table of Contents​
2 
Study Protocol​
3 
Objectives:​
3 
Design:​
3 
Methods:​
3 
Statistical Analysis Plan​
4 
 
 
 

Study Protocol 
Objectives 
The goal of this clinical trial is to learn if N-Acetylcysteine drug works to protect kidney 
function in adults patient with cancer. Kidney function will be measured by laboratory parameter 
using urine sample (KIM-1 urine) and blood sample (serum creatinine). The main questions it 
aims to answer are: 
1.​ Does N-Acetylcysteine lower the level of KIM-1 (Kidney Injury Molecule) in patients 
urine indicating kidney function protection? 
2.​ Does N-Acetylcysteine lower the level of creatinine in patients blood indicating kidney 
function protection? 
 
 
Design: 
​
This is an interventional study with a double-blind randomized clinical trial approach 
focusing on phase 2/ phase 3 treatment study. Subjects that meet the eligibility criteria will be 
recruited and randomized into two groups, the treatment or the control group. 
 
Methods: 
Location. This study will be conducted in Cipto Mangunkusumo Hospital, Central 
Jakarta, Indonesia, from September 2025 until August 2027. 
Sample and Recruitment.Patients that meet the eligibility criteria mentioned below will 
be recruited. Patients with the minimum age of 18 years, with no maximum age, without any sex 
or gender restriction are allowed to participate in this study.  
The Inclusion Criteria: 
• Patient with cancer/ malignancy proven by histopathological examination 
• Patient with GFR ≥60 ml/mins/1,73 m² 
• Patient with normal complete blood count and liver function test result 
• Patient with good performance status (Karnofsky score ≥80) 
• Patients with cisplatin based chemotherapy 
The Exclusion Criteria: 
• Patient that can not tolerate N-Acetylcysteine usage 
• Patient with history of hypersensitivity to N-Acetylcysteine 
• Patient that given other potentially nephrotoxic drug, such as furosemide, 
non-steroidal anti-infammatory drugs, aminoglycosides, amphotericin B, 
cephalosporine 
• Patient that given other chemotherapy drug, such as permetrexed, 
ifosfamide, gemcitabin, bevacizumab, cetuxsimab 
• Patient with history of malignant or uncontrolled hypertension 
• patient with congestive heart failure, kidney structure abnormality, and 
acute infection 

• Pregnant or lactating women 
• Patient refusing to participate in the research 
​
Procedure. Patients that are willing to participate and meet all the eligibility criteria will 
be given the information about the aims of the study, the procedures they will undergo, and will 
be asked to fill in the informed consent form. If the participants were unable to read and/or write, 
or due to their age or other reasons unable to make the decision for themselves, a legal guardian 
will be informed and will be asked to fill the informed consent form instead. All the participants 
then will undergo clinical examination including history taking and physical examination. They 
will also have their sample (blood and urine) taken at three different times: before they received 
the intervention, 1 week after the intervention, and 3 weeks after the intervention. The urine 
sample that will be taken is the morning urine and it will be placed in a urine pot. Meanwhile, the 
blood sample from veins will be placed into two tubes, the purple one that contains EDTA and 
the green one that contains heparin. All of the samples will be sent to the laboratory for further 
analysis. 
​
Then, all of the participants will be randomized into two groups, the intervention and the 
control group. The intervention group will be given N-Acetylcysteine tabs 1200 mg twice a day 
for 7 days, the day before cisplatin chemotherapy, on the chemotherapy day, and five days after 
the chemotherapy. Meanwhile, the control group will be given the placebo and cisplatin 
chemotherapy. All of the participants in the two groups will be given the same hydration regimen 
before the chemotherapy session, which is 500 mL  normal saline 0,9%  for 6 hours and will be 
continued during the session. 
​
The investigator team will be evaluating the adverse effects, hospitalization, and death in 
all of the participants during the research. If a participant is experiencing adverse effects during 
the research, they will be asked to come to our hospital for further evaluation. The research team 
then will treat them as seen appropriate and will evaluate whether they were eligible to continue 
participating in this study. Another informed consent will be asked if necessary. All of the 
participants will be asked to come for examination and sample collection 1 week and 3 weeks 
after the intervention and chemotherapy session. 
​
 
 
 
 

Statistical Analysis Plan 
 
The participants' data will be recorded in a case report form before it will be uploaded into the electronic 
database. Data will be analyzed using the SPSS 27.0 version. Descriptive tests using univariate analysis 
will be conducted for the demographic data. Categoric data will be presented in number and percentage. 
Meanwhile, numeric data with normal distribution will be presented in mean and standard deviation, and 
numeric data with abnormal distribution will be presented in median, minimum, and maximum range. 
 
Comparative study will be conducted using bivariate tests of the urinary KIM-1 and serum creatinine data 
in both groups before and after the intervention. If the data were normally distributed, an independent T 
test will be conducted, but if the data were not normally distributed, a Mann-Whitney test will be 
conducted instead. The result will be interpreted as statistically significant if the p value is under 0.05 
with confidence interval 95%. All of the data from the participants that were lost to follow up, refused to 
continue, or died during the study will not be included in the analysis.