Study on the Safety of Administering Isoniazid to Systemic Lupus Erythematosus Patients to Prevent Tuberculosis
Phase: PHASE2
Conditions: Tuberculosis, Systemic Lupus Erythematosus
Sponsor: Universitas Padjadjaran

1 
 
 
 
 
 
 
STUDY PROTOCOL 
 
 
STUDY ON THE SAFETY OF ADMINISTERING ISONIAZID TO 
SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS TO PREVENT 
TUBERCULOSIS 
 
Unique Protocol ID: IPD-202402.01 
Document Date: August 1st 2022 
NCT Number: N/A 
 
 
Researcher: 
Dr. Laniyati Hamijoyo, dr., Sp.PD-KR, M.Kes 
(8830960018) 
Edhyana Sahiratmadja, dr., PhD (0011056602) 
Bachti Alisjahbana, dr., Sp.PD-KPTI, PhD 
(8849720016) 
Guntur Darmawan, dr., Sp.PD 
 
 
 
 
PADJADJARAN UNIVERSITY 
2024 
 
 
 
 
 

2 
 
 
 
 
 
 
 
STUDY PROTOCOL 
 
 
STUDY ON THE SAFETY OF ADMINISTERING ISONIAZID TO 
SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS TO PREVENT 
TUBERCULOSIS 
 
Researcher: 
Dr. Laniyati Hamijoyo, dr., Sp.PD-KR., M.Kes - Division of Rheumatology and 
Immunology, Department of Internal Medicine, Padjajaran University, Hasan 
Sadikin Hospital Bandung. 
Bachti Alisjahbana, dr, Sp.PD-KPTI, PhD - Division of Tropical and Infectious 
Diseases, Department of Internal Medicine, Padjajaran University, Hasan Sadikin 
Hospital Bandung. 
Edhyana Sahiratmadja, dr., PhD - Division of Molecular Biology, Department of 
Biomedical Sciences, Padjajaran University, Hasan Sadikin Hospital Bandung. 
Guntur Darmawan, dr., Sp.PD - Department of Internal Medicine, Krida Wacana 
Christian University. 
 
 
Aim 
This study aims to prove that the administration of Isoniazid (INH) in the 
prevention of Tuberculosis (TB) in patients with Systemic Lupus Erythematosus 
(SLE) is safe against liver toxicity and disease recurrence. 
 
Research Design 
An open-label, randomized, controlled, prospective cohort study evaluating 
two groups of SLE patients, those receiving INH and pyridoxine for nine months 
and those not receiving both drugs. Signs and symptoms of drug-induced 
hepatotoxicity and degree of SLE disease activity were assessed monthly for the 
first three months (months 1/2, 1, 2, and 3), and then continued every three 
months for up to one year (months 6, 9, and 12). 

3 
 
 
Introduction 
Systemic Lupus Erythematosus (SLE) is a highly complex chronic 
autoimmune disease that affects multiple organs.1 The course of the disease is 
influenced by many things, one of which is infection.2 SLE patients are more 
susceptible to infections, due to their disease activity as well as the use of 
immunosuppressant drugs and glucocorticoids.3 One of the infections that mainly 
affects SLE patients is Tuberculosis (TB) infection,4 especially patients living in 
Asian areas that are endemic to TB.5 
TB infection increases the morbidity and mortality of SLE patients, causing 
more severe disease and death in SLE.6-17 The World Health Organization 
(WHO) has established guidelines for TB prevention in HIV patients.18 Efforts to 
prevent TB have been made in HIV patients by administering Isoniazid (INH) 
prophylaxis and found to significantly reduce the incidence of TB in HIV patients 
by 35%, with good safety data and no significant increase in drug side effects.19 
Prevention of TB in SLE is controversial, and no guidelines have been issued 
on the subject. An Indian study found an 82% reduction in the incidence of TB in 
SLE patients with INH prophylaxis.20 However, retrospective studies in Hong 
Kong and Korea found no significant difference between those given and those 
not given prophylaxis.13,21 No studies have specifically examined the safety of 
INH prophylaxis in SLE patients. Research is needed on the safety of INH in SLE 
patients, especially in terms of toxicity to the liver and its effect on disease 
recurrence, before further research on its effectiveness in preventing TB in SLE 
patients. 
 
 
 
 
Research Design and Subjects 
This is a randomized controlled clinical study involving SLE patients at the 
Rheumatology Polyclinic, Department of Internal Medicine, Padjadjaran 
University, Hasan Sadikin General Hospital Bandung, 

4 
 
Screening for TB and impaired 
liver function: 
Informed Consent 
History review 
Physical Examination 
Laboratory examination 
Chest X-ray 
SLE patients attending the RSHS 
rheumatology clinic and enrolled as 
Lupus Registry participants, with 
remitted or mild SLE disease activity. 
 
The diagnosis of SLE is based on the 1997 ACR criteria or 2012 SLICC 
criteria. The screening included informed consent, history taking, physical 
examination, chest X-ray, and laboratory examination (mainly SGOT/SGPT, 
HBsAg, anti HCV Total). The examination was conducted to ensure that the 
subjects did not suffer from active TB, and or impaired liver function. Subjects 
who meet the inclusion criteria will be randomly divided into two groups, the 
treatment group receiving INH 5 mg/kg/day (maximum 300 mg/day) and 
pyridoxine 10 mg/day, and the control group receiving neither drug. Routine SLE 
medications will be continued throughout the study and recorded at each visit. 
The research design is depicted through the chart below: 
Received INH 300 mg/day and 
Pyridoxine 10 mg/day for nine 
months 
Routine SLE medication 
continued and routinely 
recorded at each visit 
    Received Placebo 
SLE patients who fulfil the inclusion 
criteria 
Monitor SGOT/SGPT and SLE 
disease activity after two weeks, 
continuing monthly in the first three 
months (months 1/2, 1 2,3) then every 
three months for up to one year 
(months 6, 9, 12). 
Exclusion if: 
• 
Impaired liver function, 
including hepatitis B/C 
positivity 
• 
History of allergy to INH 
• 
Pregnancy 
• 
Malignancy 

5 
 
 
Inclusion and Exclusion Criteria 
Inclusion Criteria 
• SLE patients who do not have signs and symptoms of active TB (pulmonary 
and extrapulmonary), 
• SLE patients who are not on TB treatment, 
• SLE patients with no history of TB, 
• SLE patients who are in remission or low disease activity state (LLDAS), with 
a history of stable SLE treatment in the last three months and have good liver 
function, 
• Agree to fully participate in this study. 
 
 
Exclusion Criteria 
• SLE patients who have previous liver dysfunction, including hepatitis B or 
hepatitis C, 
• SLE patients who have a history of allergy to INH, 
• SLE patients with malignancy, 
• SLE patients who are pregnant. 
 
 
 
 
 

6 
 
 
Variables 
 
VARIABLES 
DEFINITION 
ASSESSMENT 
OUTPUTS 
DATA TYPE 
Systemic 
Lupus 
Erythematosus 
(SLE) 
ACR 1997 or SLICC 
2012 criteria22,23 
History 
review, 
physical 
examination, 
laboratory 
examination 
Yes/No 
Nominal 
 
 
Age 
Age at the time of 
study 
History review 
Year 
Numerical 
 
Duration of SLE 
Duration from 
diagnosis of SLE to 
inclusion in the study. 
History review 
and medical 
record 
confirmation 
Month 
Numerical 
 
Isoniazid (INH) 
preventive 
therapy 
INH 5 mg/kg/day, 
max 300 mg/day for 
nine months 
History review 
Yes/No 
Nominal 
 
Tuberculosis 
Active TB. 
History 
review, 
physical 
examination, 
Chest X-
Ray,  
and/or 
AFB/RMT 
examination. 
Yes/No 
Nominal 
 
SLE disease 
activity 25 
Based on the SLE 
disease activity index 
(SLEDAI-2K) score: 
• 
0 = remission 
• 
1-5 = mild 
• 
6-11 = moderate 
• 
12 = severe 
History 
review, 
physical 
examination, 
laboratory 
examination 
As per score 
Nominal 
 
Changes in SLE 
disease 
activity26 
Based on change in 
SLE disease activity 
index (SLEDAI-2K) 
score. Change in 
score: 
• 
increased ≥ 3 
= relapse 
• 
decreased ≥ 3 = 
improved 
• 
increased but < 3 
= active persistent 
History 
review, 
physical 
examination, 
laboratory 
examination 
As per score 
Nominal 
 
Drug-induced 
hepatotoxicity 
(INH) 
Increase of more than 
twice the upper limit of 
normal SGOT/SGPT 
values and 
improvement after 
drug withdrawal27 
History 
review, 
physical 
examination, 
laboratory 
examination 
Yes/No 
Nominal 

7 
 
 
R value28 
Values used to 
distinguish the type of 
damage in drug- 
induced 
hepatotoxicity. 
R = (SGPT value / 
upper limit of normal 
SGPT value) / (ALP 
value / upper limit of 
ALP value). 
Laboratory 
examination 
As per the result 
value 
Numerical 
Types of 
damage in 
drug-induced 
hepatotoxicity28 
Type of damage: 
• Hepatocellular 
(SGPT ≥3 upper 
limit of normal 
values and R ≥ 5). 
• Cholestatic (ALP ≥2 
upper limit of 
normal value and R 
≤ 2). 
• Mixed (SGPT ≥3 
upper limit of 
normal, ALP ≥2 
upper limit of 
normal, and 2 < R < 
5). 
Laboratory 
examination 
According to the 
type of damage 
Nominal 
Severity of 
drug-induced 
hepatotoxicity28 
• Grade 0 (No Liver 
Injury): the patient 
can tolerate the 
drugs and there 
are no signs and 
symptoms of 
hepatotoxicity. 
• Grade 1 (Mild Liver 
Injury): elevated 
SGPT and/or ALP 
values, total 
bilirubin <2.5 upper 
limit of normal (2.5 
mg/dL or 42.75 
μmol/L), INR <1.5. 
Most patients show 
adaptive processes 
to liver damage. It 
may be 
accompanied or 
without symptoms, 
such as fatigue, 
nausea, anorexia, 
right upper 
abdominal pain, 
jaundice, itching, 
skin redness, or 
weight loss. 
• Grade 2 (Moderate 
Liver Injury): 
elevated SGPT 
and/or ALP values, 
History review, 
physical 
examination, 
laboratory 
examination 
As per grade 
Ordinal 

8 
 
 
 
with total bilirubin 
≥2.5 upper limit of 
normal or INR 
≥1.5. Symptoms 
and signs of 
impaired liver 
function become 
more apparent. 
• Grade 3 (Severe 
Liver Injury): 
elevated SGPT 
and/or ALP, total 
bilirubin ≥5 upper 
limit of normal (5 
mg/dL or 85.5 
μmol/L) with or 
without INR ≥1.5. 
Symptoms and 
signs of hepatic 
impairment are 
obvious, indicating 
the need for 
hospitalisation. 
There are no signs 
and symptoms of 
hepatic 
encephalopathy. 
• Grade 4 (Acute 
Liver Failure): 
evidence of blood 
clotting disorders 
with INR ≥1.5 or 
PTA <40%, signs 
and symptoms of 
hepatic 
encephalopathy, 
and total bilirubin 
values ≥10 upper 
limit of normal (10 
mg/dL or 171 
μmol/L) or an 
increase in total 
bilirubin values 
≥1.0 mg/dL (17.1 
μmol/L) per day for 
26 weeks after the 
onset of drug- 
induced 
hepatotoxicity. 
Patients may 
develop ascites 
and other organ 
dysfunction. 
• Grade 5 (Lethal): 
death caused by 
drug-induced 
hepatotoxicity. 

9 
 
 
Unexpected 
events29 
• Grade 1 Mild; 
asymptomatic or 
mild symptoms 
only; clinical 
observation or 
diagnosis only; 
intervention not 
indicated. 
• Grade 2 Moderate; 
minimal, local or 
non-invasive 
interventions are 
indicated; limitation 
of daily activities 
based on age. 
• Grade 3 Severe or 
medically 
significant, but not 
life threatening; 
indication for 
hospital admission; 
limitation of 
independent daily 
activities. 
• Grade 4 Life- 
threatening; 
indication for 
rapid/immediate 
intervention. 
• Grade 5 Lethal; 
associated with an 
adverse event. 
History review, 
physical 
examination, 
laboratory 
examination 
As per grade 
Ordinal 
Acid Fast 
Bacilli (AFB)30 
Staining technique to 
see acid fast bacilli 
(Mycobacterium 
tuberculosis) from the 
sample taken 
Laboratory 
examination 
Positive/negative 
Nominal 
Rapid 
Molecular Test 
(RMT)31 
Rapid PCR 
(Polymerase Chain 
Reaction) testing 
using the GeneXpert 
platform that can 
detect TB bacteria 
Laboratory 
examination 
Positive/negative  
Nominal  
 
Research Duration and Time 
This research was conducted from August 2022 to December 2024. 
 
 
Sample size calculation 
The sample size calculation was carried out based on INH prophylaxis studies 
conducted in HIV patients, obtained the risk of drug reaction events of RR 1.2, so 
that with a confidence level of 95%, power 80%, and effect size 0.5, the sample 

10 
 
 
size of each group was 27 people, plus 10% to 30 people. Thus, the total number 
of patients involved is 60 people who will be divided into two groups. 
 
Data Analysis 
This study was conducted to assess the safety of INH drug administration in 
SLE patients by analyzing the increase in SGOT/SGPT values and assessing 
SLE disease activity measured using SLEDAI. Both will be assessed after two 
weeks of drug or placebo administration, followed by monthly for the first three 
months (months 1, 2, 3), then every three months until one year (months 6, 9, 
12). Statistical tests used were t-test and/or chi-square by comparing two 
treatment groups. Results were considered significant when the p value was ≤ 
0.05. Data processing was performed with SPSS version 26 and Stata version 
13. 
 
Outputs 
The incidence of TB in SLE patients, especially in endemic countries, is high 
at 11.4%32. This rate is much higher than the normal population. The 
administration of isoniazid (INH) has been recommended for TB prophylaxis in 
HIV patients. However, until now there has no guideline or agreement on the 
administration of INH as TB prophylaxis in SLE patients. Studies of INH as TB 
prophylaxis in SLE patients have shown mixed results. Safety is one of the 
aspects considered, given the risk of drug-induced hepatitis. Therefore, a study to 
evaluate the safety of TB prophylaxis therapy with INH in SLE patients is very 
important. Furthermore, this study can serve as a base for further research to 
evaluate the effectiveness of TB prophylaxis therapy with INH in SLE patients. 

11 
 
 
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14 
 
Appendix 1 
 
Gantt Chart Timeline Table 
 
Type of Activity 
Year 1 
Year 2 
4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 
Subject Screening 
Subject Recruitment 
Inspection 
Data Analysis 
Report Generation 
Publication of Results 

15 
 
Appendix 2 
 
CRF INH Safety Study in SLE Patients: 
Initial Screening 
 
Subject Number 
 
MR Number: □Inpatient  
□ Rheumatology Clinic  
 
Full Name:  
 
Gender: □F/ M □ 
Date of Birth (day/month/year):  
 
/  
/ 
 Tel/Phone:  
 
 
Full Address:  
 
  
 
 
 
 
Occupation:  
 
 Education:  
 
Ethnic:  
 
Marital Status:  
Date of SLE diagnosis (month/year):     /    
 
Visit 0 Date (day/month/year):  
/ 
/ 
 
 
Clinical (TB, SLE, Liver Disease, Pregnancy) 
Routine Lab data screening 
Chest X-Ray 
History review 
History: 
• Tuberculosis (TB): □Ever□ Never□ Don't Know 
• Liver/Liver Disease: □Ever□ Never□ Don't Know 
• Allergy to INH: □ Yes□ No□ Don't Know 
• Malignancy/Cancer: □ Yes□ No□ Don't Know 
• Currently on TB treatment: □ Yes□ No□ Don't Know 
• Currently pregnant□ Yes□ No□ Don't Know 
Hb 
Ht 
Leukocytes 
Platelets 
Count 
Type 
Basophils 
Eosinophils 
Neutrophil Rod 
Neutrophil Segment 
Monocytes 
Lymphocytes 
ESR 
SGOT 
SGPT 
HBsAg 
Anti HCV 
Creatinine 
Physical Examination 
Urinalysis 
Proteinuria 
Erythrocytes 
Leukocytes 
Cylinders 
 
*When Clinically Suspicious of TB 
Date 
Chest X-Ray 
AFB 
RMT 
Active TB: □ Yes (Clinical/Bacteriological) □ No 
SLEDAI 
Parameters 
Score 
Total 
Parameters 
Score 
Total 
Seizures 
8 
Arthritis 
4 
Psychosis 
8 
Myositis 
4 
Organic Brain Syndrome 
8 
Cylinders 
4 
Visual Impairment 
8 
Haematuria 
4 
Cranial Nerve Abnormalities 
8 
Proteinuria 
4 
Lupus Headache 
8 
Piuria 
4 
Cerebrovascular 
8 
Pleuritis 
2 
Vasculitis 
8 
Pericarditis 
2 
New Malar Rash 
2 
Low complement 
2 
Alopecia 
2 
Anti-dsDNA increased 
2 
New/recurrent ulcers 
2 
Thrombocytopenia 
1 
Fever 
1 
Leukopenia 
1 
SLEDAI Total Score:  
□ 0 (Remission)□ 1-5 (Mild)□ 6-11 (Moderate) □ 12 (Severe) 
 
SLE medications: Take SLE medications regularly: □ Yes □ No 
Medicine 
Dosage 
Start date 
Stop date 
□ Prednisone/equivalent 
mg/day 
□ Pulse Steroids 
mg/day 
□ HCQ/CQ 
mg/day 
□ Methotrexate 
mg/week 
□ Azathioprine 
mg/day 

16 
 
□ MMF 
mg/day 
□ Mycophenolic acid 
mg/day 
□ Leflunomide 
mg/day 
□ Cyclosporin 
mg/N 
□ Tacrolimus 
mg/day 
□ Cyclophosphamide 
□NIH□ EuroLupus 
□ Rituximab 
□ More 

17 
 
CRF INH Safety Study in SLE Patients: Follow Up 
 
Subject Number 
No Drug Study 
 
MR Number: □Inpatient  
□ Rheumatology Clinic   
 
Full Name:  
 
Gender: □F/ M □ 
Date of Birth (day/month/year):  
/ 
/ 
 Tel/Phone:  
 
 
Visit 
( 
months from visit  
) Date (day/month/year):  / 
/ 
 
Take medication regularly: □ Yes□ No 
 
Clinical 
Laboratory 
History review 
Hb 
□ Fever □ Malaise □ Fatigue □ Abdominal Pain □ Nausea 
Ht 
□ Vomiting□ Icteric 
Leukocytes 
□ Others: 
Platelets 
Basophils 
Eosinophils 
Count 
Neut Rod 
Type 
Neut Segment 
Monocytes 
Lymphocytes 
ESR 
Physical Examination 
SGOT 
SGPT 
Creatinine 
Urinalysis 
Proteinuria 
Erythrocytes 
Leukocytes 
Cylinders 
 
SLEDAI Score: 
SLEDAI Total Score:  
□ 0 (Remission)□ 1-5 (Mild)□ 6-11 (Moderate) □ 12 (Severe) 
SLE Disease Activity: □ Relapse□ Improving□ Persistently Active□ Remission 
Elevated SGOT/SGPT 2x Upper limit of normal values: □ Yes□ No 
 
Liver function disorders: □ Hepatocellular□ Cholestatic□ Mixed 
Severity: 
□ 0 (No Liver Injury) 
□ 1 (Mild Liver Injury) 
□ 2 (Moderate Liver Injury) 
□ 3 (Severe Liver Injury) 
□ 4 (Acute Liver Failure) 
□ 5 (Lethal) 
 
Management of Drug-Induced Hepatoxicity 
□ INH discontinue 
□ Continue INH Administration 
□ Other medications:  
  
 
 
 
 
Drug-induced hepatotoxicity outcomes 
 
 
 
 

18 
 
CRF INH Safety Study in SLE Patients: 
SLE recurrence 
 
 
Subject Number 
 
Full Name:  
Gender: □F/ L □ 
Date of Birth (day/month/year):  
/ 
/ 
 Tel/Phone:  
 
 
Visit 
( 
months from visit  
) Date (day/month/year):  
/ 
/ 
 
SLEDAI score (at time of screening): _____□ Remission □ Mild □ Moderate  □Severe 
 Previous SLEDAI scores:  
 
Diagnosis of SLE Recurrence 
 
Clinical (SLE) 
History review 
Physical Examination 
Management of SLE Recurrence (based on rheumatologist's judgement) 
□ INH discontinue 
□ Continue INH 
□ Changes in SLE medications (see CRF for SLE medications, any changes should be noted on the CRF) 
□ Other medications: 
  
 
 
 
 
SLE Recurrence Outcome 
 
Outputs 
SLEDAI Score 
Date (day/month/year) 
□ Relapse 
□ Improving 
□ Active Persistent 
□ Remission 
□ Died 
□ Others: 

19 
 
 
 
 
CRF INH Safety Study in SLE Patients: 
SLE medications 
 
No Subject  
 
Full Name:  
Gender: □F/ M □ 
Date of Birth (day/month/year):  
/ 
/ 
 Tel/Phone:  
 
 
Visit 
( 
months from visit  
) Date (day/month/year):  
/ 
/ 
 
Take SLE medication regularly: □ Yes □ No 
 
SLE medications 
Medicine 
Dosage 
□ Prednisone or equivalent 
mg/day 
□ Pulse Steroids 
mg/day 
□ HCQ/CQ 
mg/day 
□ Methotrexate 
mg/week 
□ Azathioprine 
mg/day 
□ MMF 
mg/day 
□ Mycophenolic acid 
mg/day 
□ Leflunomide 
mg/day 
□ Cyclosporin 
mg/N 
□ Tacrolimus 
mg/day 
□ Cyclophosphamide 
□NIH□ Euro Lupus 
□ Rituximab 
□ Belimumab 
□ Others: 
 
 
 

20 
 
 
 
 
Appendix 3. Informed Consent 
INFORMED CONSENT 
 
 
STUDY ON THE SAFETY OF ADMINISTERING ISONIAZID TO 
SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS TO 
PREVENT TUBERCULOSIS 
 
Unique Protocol ID: IPD-202402.01 
Document Date: August 1st 2022 
NCT Number: N/A 
 
 
Researcher: 
Dr. Laniyati Hamijoyo, dr., Sp.PD-KR, M.Kes 
(8830960018) 
Edhyana Sahiratmadja, dr., PhD 
(0011056602) Bachti Alisjahbana, dr., Sp.PD-
KPTI, PhD (8849720016) 
Guntur Darmawan, dr., Sp.PD 
 
 
 
 
PADJADJARAN 
UNIVERSITY 
 
 
 
 
 
 
 
 

21 
 
 
INFORMATION 
" Study on the Safety of Administering Isoniazid to Systemic Lupus Erythematosus 
Patients to Prevent Tuberculosis " 
 
I am Dr. Laniyati Hamijoyo, dr., SpPD-KR, I am a rheumatologist at the Faculty of Medicine, 
Padjadjaran University / Hasan Sadikin Hospital Bandung. My team and I are conducting a study to 
determine  safety of Isoniazid (INH) to prevent Tuberculosis (TB) in Systemic Lupus Erythematosus 
(SLE) patients. SLE patients are susceptible to TB disease. This is due to their autoimmune condition, 
as well as the corticosteroid and/or immunosuppressant drugs taken by the patient. Indonesia has 
the second highest number of TB cases in the world and remains a TB endemic country to date. TB 
suffered by people with SLE can cause severe problems, especially in terms of disease recurrence 
(lupus becomes active) which can worsen the patient's condition. Therefore, TB should be 
prevented. One form of prevention that can be done is the administration of Isoniazid (INH) therapy 
for nine months. Through this, SLE patients are expected to avoid TB. We invite you to participate in 
this study. Your participation in this study is voluntary, so you can decide whether or not to 
participate. 
 
Research Objectives: 
The aim of this study was to determine the safety of Isoniazid (INH) therapy to prevent TB in SLE 
patients. 
 
Why the subject was chosen: 
You were selected as a respondent because you met the criteria intended by the researchers, namely 
SLE patients with a low degree of disease activity/remission, not currently undergoing TB therapy, no 
history of TB, no symptoms/signs of active TB disease, no liver function disorders, no history of allergy 
to INH drugs, and willing to participate in this study until completion. 
 
Procedure: 
This study will be conducted by taking blood samples and performing Chest X-Ray for initial 
screening. If you meet the criteria, you will be divided into two groups. One group will receive INH 
therapy at a dose of 5 mg/kg BW/day (maximum 300 mg) and vitamin B6 10 mg/day, while the other 
group will receive placebo (no INH/Vitamin B6). The drugs will be consumed for nine months. The side 
effects of the drugs and lupus disease activity will be monitored through monthly blood tests in the 
first three months (months 1/2, 1, 2, 3) and every three months until month 12 (months 6, 9, 12). If 
necessary, a chest X-Ray and/or sputum examination will be done to confirm whether you have TB 
or not. 

22 
 
Risk and inconvenience: 
Possible risks include discomfort during blood collection, hematoma (blue-black bruising) at the site 
of blood collection and exposure to X-Ray radiation. Other possible risks include nausea, jaundice, 
bloating, and impaired liver function. 
 
Benefits (direct to subject and general): 
Public benefit: This study may serve as a guide for physicians treating SLE patients to provide TB 
preventive therapy, especially for those living in TB-endemic areas. 
Direct benefits obtained by the subject: knowing the status of disease activity, getting screened for TB, 
and obtaining TB prevention therapy. 
 
Alternative procedure: 
None. 
 
Data confidentiality: 
We will guarantee the confidentiality of information relating to your identity and will not be known 
by unauthorized persons. The results of this study will be published without mentioning your identity. 
 
Estimated number of subjects to be included: 
The subjects to be included in this study were 60 SLE patients. 
 
Volunteerism: 
Your participation in this study is voluntary. 
 
Subject Participation Period: 
This research is planned to take place August 2022 to December 2024. If you have followed the study 
completely, your participation in this study is considered complete. 
 
Subjects may be excluded/resigned from the study: 
If during the implementation of the study you want to withdraw or do not want to continue, then you 
are allowed to withdraw before the data collection process is carried out. 

23 
 
Possible financing from health insurance companies or researchers: 
No insurance will be provided to you in this study. If side effects occur due to the INH medication, you 
will be closely monitored and treated for any possible side effects, such as nausea, vomiting or itching. 
If hospitalization is required, all treatment costs will be the responsibility of the researcher. 
 
Incentives and compensation: 
If you are willing to participate in this study, you will be compensated in the form of transport money 
totaling IDR 50,000 per visit (six visits) until the completion of the study. 
 
Question: 
If there are any questions regarding this study, respondents can contact the researcher at the 
rheumatology clinic of Dr. Hasan Sadikin Hospital. 
 
Researcher: 
Dr. Laniyati Hamijo, dr., SpPD-KR 
Mobile Number: +6281223032863 
 
Research Assistant: 
dr. Naurah Alzena Hana Dhea 
Mobile Number: +6281312126312 

24 
 
APPROVAL AFTER EXPLANATION  TO 
PARTICIPATE IN THE RESEARCH 
(INFORMED CONSENT) 
 
I have read or obtained an explanation, fully realize, understand, and understand the purpose, benefits, 
and risks that may arise in the research, and have been given the opportunity to ask questions and 
have been answered satisfactorily, as well as at any time can withdraw from participation, then I agree 
/ do not agree*) participate in this study, entitled: 
 
"Study on the Safety of Administering Isoniazid to Systemic Lupus Erythematosus Patients 
to Prevent Tuberculosis" 
 
I voluntarily choose to participate in this study without any pressure. I will be given a copy of the 
explanation sheet and signed consent form for my records. 
I agree: 
Yes/No *) 
 
Date 
Signature (if   not   possible, 
thumbprint can be used) 
Participant Name: 
Age: 
Address: 
Researcher Name: 
Witness Name: 
 
*) cross out unnecessary 
 
 
 
 

25 
 
Appendix 4. Ethical Approval