The Effect of Allopurinol on Malondialdehyde, Nitric Oxide, Kidney Injury Molecule-1 Urine Levels, Resistive Index and Renal Elastography in Kidney Stone Patients After Extra Corporeal Shockwave Lithotripsy
Phase: PHASE4
Conditions: Kidney Calculi
Sponsor: Sanglah General Hospital

STUDY PROTOCOL, STATISTICAL ANALYSIS PLAN (SAP) AND INFORMED
CONSENT FORM (ICF)
Study Title : The Effect of Allopurinol on Malondialdehyde, Nitric Oxide,
Kidney Injury Molecule-1 Urine Levels, Resistive Index and Renal
Elastography in Kidney Stone Patients After Extra Corporeal Shockwave
Lithotripsy
Principal Investigator: Kadek Budi Santosa, MD, Urologist
Urology Department, Sanglah General Hospital
Human Subjects Review Approved Dated : 03.08.2020
31st August 2020

STUDY PROTOCOL
1.1. Study Design and Patient Selection
This study was designed as a randomized, double-blind placebo-controlled trial to
assess the effect of allopurinol administration in reducing tubular damage, vascular
dysfunction and focal zone biophysical changes in the kidney due to ESWL.
Patients were randomly assigned to the intervention and placebo groups in this
clinical study. The study group was formed of patients with kidney stone who
undergo ESWL.
1.2. Process and Intervention
Patients with kidney stones who will undergo ESWL were randomized into 2 groups.
Group 1 was given allopurinol, and group 2 was given a placebo. Allopurinol 300 mg
was administered orally for a total of 3 days, starting from the day before ESWL.
Malondialdehyde (MDA), nitric oxide (NO), kidney injury molecule-1 (KIM-1) in
urine were measured by technique quantitative double antibody sandwich direct
ELISA before ESWL, continued two hours, and 24 hours after ESWL. Changes in the
interlobar artery resistive index (RI) were assessed together with measurements of
shear wave velocity (SWV) values in the renal focal zone before ESWL, followed by
two weeks, and four weeks after ESWL.
1.3. Safety Evaluation
If there was any drug side effects or serious adverse events(SAE), the subjects were
reported to the ethics committee as soon as possible, less than 24 hours from the first
time they were discovered, and actions were carried out as quickly as possible until
the series of events ends. SAE was written in detail on the SAE form, including the
following; when it was first discovered, the manifestation of the incident, the
conditions before the incident, the handling of the event, and the outcome.
If the subject experiences side effects such as allergic reactions (redness of the skin,
swelling of the eyes or mouth) and severe gastrointestinal disturbances (vomiting,
diarrhea), the subject will be excluded from the analysis. The subject will also be
excluded from the analysis if the subjects experience complications related to ESWL

procedure such as ureteral obstruction, pain (VAS > 5), or there were signs of
infection. Subjects will be evaluated when visiting the hospital according to schedule,
telephone contact, or by making a home visit.
1.4. Sample Size
The Population of the study consisted of patients with kidney stones who will undergo
ESWL. The sample size was calculated based on the statistical diagnosis of the study
which is, comparative analysis of independent two groups. A total of 70 subjects were
planned to be included in the study, 35 of which were intervention while the rest were
placebo. Patients were randomly assigned to both groups in this study.
1.5. Ethical Approval
Approval for the study was granted by the Research Ethics Committee Faculty of
Medicine, Udayana University(Number: 1637/UN14.2.2.VII.14/LT/2020). Verbal and
written informed consent was obtained from all subjects in the study.
Author Contributions
Conflict of Interests
The Authors have no conflict of interests to declare
Acknowledgements
The authors thank all those participated in this study.
Financial Disclosure

STATISTICAL ANALYSIS PLAN (SAP)
Data collected in this study were analysed statistically using
SPSS for Windows
software
25.
Data
were
analysed
by
descriptive
statistics
to
describe
the
characteristics of the subjects based on the treatment group and presented in the form
of a distribution table. The compatibility of the variables on the numerical data scale
uses the average comparison with the independent t-test. The categorical-scale
variables used the proportion comparison with chi-square test. The limit value of
significance was set at 0.05. The normality data assessment in this study is based on
the central limit theorem, where the sample size in each group more than 30 makes
the z distribution close to the t distribution and the data will be normally distributed.
Bivariate and Multivariate analyses were performed using repeated measure ANOVA
to control covariates. The value of the limit of significance is set to 0.05.

INFORMED CONSENT FORM (ICF)
We are looking forward to your participation in this clinical study that held by dr.
Kadek
Budi
Santosa,
Urologist,
entitled
“The
Effect
of
Allopurinol
on
Malondialdehyde, Nitric Oxide, Kidney Injury Molecule-1 Urine Levells, Resistive
Index and Renal Elastography in Kidney Stone Patients After Extra Corporeal
Shockwave Litothrypsi”.
You have kidney stones who are going to undergo ESWL, thus were asked to
participate in this study. Please read this information prior to determine if you are
going to participate or not. Please don’t be hesitate to ask if there is something unclear.
If you decide to participate in this study, we expect you will follow the instruction
given.
This study is held to evaluate if administration of antioxidants, allopurinol, will be
able to prevent or reduce kidney damage due to ESWL. Allopurinol itself is already
available in the market and both its efficacy and safety have been proven.
This study will include 80 subjects. You will be randomized to two groups. One group
will get allopurinol 300mg while the other group will get placebo. Both you and the
doctor do not know which drug you get. The drug is given in three capsules, which is
consumed one day and one hour prior to ESWL, followed by one day after ESWL.
Urine examination will be done one hour prior to ESWL, followed by two hours and
one day after ESWL. Ultrasound examintation will be done one hour prior to ESWL,
followed by two weeks and one month after ESW.
Allopurinol may give side effects of nausea, vomiting or diarrhea, this drugs may also
cause alergy. If those happen, the doctor will stop the medication and hold until you
get better.
If any damage due to this study happen, you will be given help and it is free of charge.
You will follow health protocol equipped by standard personal protective equipment
given by the doctor through the process in the hospital.
This participation is voluntary. You may object to participate or quit anytime of this
study. In case you object to participate, you keep getting the treatment according to
protocol. The doctor will exclude your participation if the instruction is not followed.

The data collected in this study will be kept anonymously. Only the researcher knows
your data. This study result may be published in any scientific forum, health magazine,
or international journal without disclosing subject’s identity.
The health worker who appointed by government organization will make sure your
medical history is confidential and this study is going well. It will be done with your
consent and by signing this form, subjects have understood and given the consent.
If subject find any harm in this participation, thus compensation will be discussed
between the subject and the person in charge of this study.
Any harms or if there is any question regarding this study, please contact: dr. Kadek
Budi Santosa, Urologist at Department of Urology Sanglah Hospital, Cell phone
081339977799 or Sanglah General Hospital (0361) 227912

All the explanation above has been delivered to me and all of my consideration has
been answered by the doctor. I understand that I may ask dr. Kadek Budi Santosa,
Urologist if I need further explanation.
By signing this form, I give my consent to participate in this study.
Study’s Participant/Subject:
….……………
….……………….
Date
Signature
(Full Name : ……………………………..)
Witness:
….……………
….……………….
Date
Signature
(Full Name : ……………………………..)
Note:

Witness’ signature is required if the subject is blind or illiterate

Witness is someone who have legal relationship with subject.