TuberculosisPhase 2/3NCT06618573
Safety of Administering Isoniazid to SLE Patients to Prevent TB
A Phase 2/3 study testing Isoniazid/Pyridoxine and Saccharum Lactis in people with Tuberculosis and Systemic Lupus Erythematosus, run by Universitas Padjadjaran at 1 site in Indonesia.
Trial summary
Systemic Lupus Erythematosus (SLE) is a prototypical systemic autoimmune disease characterized by heterogeneity, multisystem involvement, and production of multiple autoantibodies. Clinical features can vary, from mild skin and joint involvement to severe and life-threatening conditions. Read more about this study
- Who is it for?
- Ages 18 to 55 years, women only
- Conditions the study is for
- Tuberculosis, Systemic Lupus Erythematosus
- What is being tested?
- Isoniazid/Pyridoxine and Saccharum Lactis
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteIndonesia
- Study dates
- 15 Aug 2022to 1 Dec 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- SLE patients with conditions of :
- No signs and symptoms of active TB
- Not under TB treatment
- No History of TB, malignancy, HIV, liver function test abnormality
- Not in pregnancy/lactation
- No other active infections
- Remission or low to moderate disease activity state
- Consented to join the study completely
Who cannot join
- SLE patients with conditions of :
- History of allergy to Isoniazid
- Chronic liver disease, including chronic hepatitis B or C virus
- Malignancy
- Pregnancy
Trial locations and contacts
1 site in 1 country.
Indonesia1 site, 1 recruiting
- Recruiting
Rumah Sakit Dr Hasan Sadikin, Universitas Padjadjaran
Bandung, West Java, 40161
Laniyati Hamijoyo, 62222040151, laniyati.hamijoyo@unpad.ac.id
About this study
Official title: Study on the Safety of Administering Isoniazid to Systemic Lupus Erythematosus Patients to Prevent Tuberculosis
Systemic Lupus Erythematosus (SLE) is a prototypical systemic autoimmune disease characterized by heterogeneity, multisystem involvement, and production of multiple autoantibodies. Clinical features can vary, from mild skin and joint involvement to severe and life-threatening conditions.
Patients with lupus are more susceptible to infections, in addition to being immunocompromised, and due to the administration of corticosteroid and cytotoxic drugs. The presence of these infections is a cause of death in lupus disease in addition to the activity of the disease itself, especially in Asia-Pacific countries. One infection that often occurs in lupus is Tuberculosis (TB).
Read more
Efforts have been made to prevent TB infection in vulnerable populations, including isoniazid (INH) prophylaxis. In 2010, World Heatlh Organization issued guidelines for HIV patients to receive INH prophylaxis to prevent TB infection. The implementation of Isoniazid Preventive Therapy (IPT) is quite cheap using INH with mild side effects.18 A meta-analysis study of INH prophylaxis in patients with HIV found that the efficacy of this prophylaxis significantly reduced TB incidence by 35% with an RR of 0.65%. In addition, INH was found to be safe, with no significant increase in drug reactions, according to a meta-analysis of prophylaxis studies in HIV patients.
However, there is no guideline for INH prophylaxis for SLE patients, as there is for HIV patients, due to lack of data on this issue.
Studies on the effectiveness of INH prophylaxis on the prevention of TB infection for SLE patients should be conducted, but before that, studies on the safety of INH therapy in SLE patients should be conducted.
Read the detailed description
Systemic Lupus Erythematosus (SLE) is a prototypical systemic autoimmune disease characterized by heterogeneity, multisystem involvement, and production of multiple autoantibodies. Clinical features can vary, from mild skin and joint involvement to severe and life-threatening conditions. The course of lupus is highly variable in the form of relapses and remissions, with mild and severe forms that can be life-threatening. Treatments for SLE includes steroids and immunosuppressants to control disease activity.
Patients with lupus are more susceptible to infections, in addition to being immunocompromised, and due to the administration of corticosteroid and cytotoxic drugs. The presence of these infections is a cause of death in lupus disease in addition to the activity of the disease itself, especially in Asia-Pacific countries. One infection that often occurs in lupus is Tuberculosis (TB).
Tuberculosis is still a problem especially in the Asian region, and Indonesia ranks 2nd with the most cases after India according to World Health Organization in 2019. TB infection is found in 10-11.4% of SLE patients in Asia. The incidence of TB in SLE is reported to range from 150/100,000 patients per year in Turkey to 2,450/100,000 patients per year in India. The annual risk of TB in SLE patients is higher than the normal population. Registry data at Hasan Sadikin Hospital Bandung showed that 11.4% or 93 out of 813 SLE patients were infected with TB after being diagnosed with SLE.
Risk factors for increased TB infection in SLE patients, in addition to SLE disease activity itself (SLEDAI score >12), renal involvement, lymphopenia, and cumulative dose of steroids used by the patient, are also due to long duration of illness and previous history of TB.
Tuberculosis is also one of the infections that cause death in SLE patients. Mortality from TB in Asian countries ranged from 5-31%. A study in the Philippines found that 14.8% of SLE patients with TB died, those who died had disseminated TB or miliary TB.
Efforts have been made to prevent TB infection in vulnerable populations, including isoniazid (INH) prophylaxis. In 2010, World Health Organization issued guidelines for HIV patients to receive INH prophylaxis to prevent TB infection. The implementation of Isoniazid Preventive Therapy (IPT) is quite cheap using INH with mild side effects. A meta-analysis study of INH prophylaxis in patients with HIV found that the efficacy of this prophylaxis significantly reduced TB incidence by 35% with an RR of 0.65%. In addition, INH was found to be safe, with no significant increase in drug reactions, according to a meta-analysis of prophylaxis studies in HIV patients.
The role of isoniazid prophylaxis for TB prevention in patients with SLE is controversial. To date, there is no consensus on prophylaxis against TB in SLE patients.
Research on this prophylaxis has been presented in an Indian study by Gaitonde et al. They found an 82% reduction in TB incidence in SLE patients with prophylactic INH at 5 mg/kg/day, with a maximum dose of 300 mg/day plus 10 mg pyridoxine (Vitamin B6) for 1 year, and no significant liver toxicity due to this drug. However, a retrospective study conducted in Hong Kong found no significant difference in TB reactivation between those who received INH compared to those who did not receive INH, while patients who received INH were reported to have more relapses of their lupus. Similarly, a retrospective study in Korea found no significant difference in patients with lupus nephritis.
The high incidence of TB in SLE patients, especially in endemic areas such as Indonesia, makes TB prevention an important endeavour. However, there is no guideline for INH prophylaxis for SLE patients, as there is for HIV patients, due to lack of data on this issue.
Studies on the effectiveness of INH prophylaxis on the prevention of TB for SLE patients should be conducted, but before that, studies on the safety of INH therapy in SLE patients should be conducted.
This study was a cohort study, with the following research design:
- LES patients attending the rheumatology clinic of RSHS and enrolled as Lupus Registry study participants, with remission or mild SLE disease activity
- Screening for TB and impaired liver function (Informed Consent, history review, physical examination, laboratory examination, Chest X-Ray) -> Exclude if have condition: Impaired liver function, including hepatitis B/C positivity, history of allergy to INH, pregnancy, malignancy
- SLE patients who fulfil the inclusion criteria divided into two groups: Received INH 300 mg/day and Pyridoxine 10 mg/day for nine months or placebo.
- Routine SLE medication continued and routinely recorded at each visit.
- 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 until one year (months 6, 9, 12).
Inclusion Criteria:
- SLE patients with conditions of:
- No signs and symptoms of active TB,
- Not under TB treatment,
- No History of TB, malignancy, HIV, liver function test abnormality
- Not in pregnancy/lactation,
- No other active infections
- Remission or low to moderate disease activity state,
- Consented to join the study completely.
Exclusion Criteria:
- SLE patients with conditions of:
- History of allergy to Isoniazid,
- Chronic liver disease, including chronic hepatitis B or C virus,
- Malignancy,
- Pregnancy.
The patients included were patients who had been diagnosed with SLE and were registered in Lupus Registry.
The study was explained and informed consent was obtained. After the patient agreed and signed Informed Consent, screening was conducted to ensure that there was no active TB, impaired liver function (SGOT/SGPT), positive Hepatitis B (HBsAg) and/or Hepatitis C (total Anti HCV), history of Isoniazid (INH) allergy, history of malignancy, and pregnancy. If any of these conditions exist, the subject will be excluded.
Eligible subjects were randomly grouped into two groups: those receiving INH 5 mg/kg/day (maximum 300 mg/day) \& Pyridoxine (Vitamin B6) 10 mg/day, or placebo. Other routine SLE medications were continued.
Sample calculations were carried out based on INH prophylaxis studies conducted in HIV patients, obtaining a risk of drug reaction events of RR 1.2, so that with a confidence level of 95% and 80% power and an effect size of 0.5, the sample size for each group was 27 people, plus 10% to 30 people. So that the total number of patients involved is 60 people divided into 2 groups.
This study was to assess the safety of INH drug administration to lupus patients assessed by the increase in SGPT and SGOT that occurred and their lupus disease activity (using the SLEDAI score) measured at month 1/2 (second week), 1, 2, 3, 6, 9 and 12. The statistical test used was a T-test comparing two groups.
The study was conducted at Dr. Hasan Sadikin Hospital, Bandung. The study was conducted from August 2022 to December 2024.
- Conditions
- Tuberculosis, Systemic Lupus Erythematosus
- Being tested
- Isoniazid/Pyridoxine, Saccharum Lactis
- Keywords
- Tuberculosis, Systemic Lupus Erythematosus
- Medical subject headings
- Tuberculosis, Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isoniazid/PyridoxineDrug
Treatment group received isoniazid 300mg and pyridoxine 10mg/day
Saccharum LactisDrug
Also called Placebo
Control group received placebo
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group | Active comparator | SLE patient at the Hasan Sadikin Rheumatology Outpatient Clinic and registered as Lupus Registry with remission or mild SLE disease activity. The diagnosis of SLE is based on ACR 1997 criteria or SLE SLICC 2012 criteria. Screening will include history review, physical examinations, chest X-Ray, laboratory test such as CBC, ALT/AST, HbsAg, total anti-HCV, complement (C3), dsDNA, creatinine serum, urinalysis (proteinuria, ACR, RBC, WBC, casts), IGRA, to assess if any subject has no active TB and no chronic liver disease.
Treatment group receiving Isoniazid 5 mg/kg/day (maximum 300 mg/day) with pyridoxine 10 mg/day.
Monitor ALT/AST and SLE disease activity after two weeks, continued monthly for the first three months (1st, 2nd, 3rd) then every three months for up to a year (6th, 9th, 12th months). Routine SLE medication is continued and routinely recorded at every visit. Receives: Drug: Isoniazid/Pyridoxine |
| Control Group | Placebo comparator | SLE patient at the Hasan Sadikin Rheumatology Outpatient Clinic and registered as Lupus Registry with remission or mild SLE disease activity. The diagnosis of SLE is based on ACR 1997 criteria or SLE SLICC 2012 criteria. Screening will include history review, physical examinations, chest X-ray, laboratory test such as CBC, ALT/AST, HbsAg, total anti-HCV, complement (C3), dsDNA, creatinine serum, urinalysis (proteinuria, ACR, RBC, WBC, casts) IGRA, to assess if any subject has no active TB and no chronic liver disease.
Control group receiving placebo.
Monitor ALT/AST and SLE disease activity after two weeks, continued monthly for the first three months (1st, 2nd, 3rd) then every three months for up to a year (6th, 9th, 12th months). Routine SLE medication is continued and routinely recorded at every visit. Receives: Drug: Saccharum Lactis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug Induce Hepatitis
Change in more than twice the upper limit of normal SGOT/SGPT values and improvement after drug discontinuation
Measured: week 2, months 1, 2, 3, 6, 9, 12
SLE disease activity
Based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. The higher the score, the worse. SLEDAI score increase in more than 3=flare
Measured: month 1, 2, 3, 6, 9, 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2024
- Study start15 Aug 2022
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- SLE patient at the Hasan Sadikin Rheumatology Outpatient Clinic and registered as Lupus Registry study participants with remission or mild SLE disease activity. Subjects fulfilled inclusion criteria will be randomly divided into two groups: treatment group receiving INH 5 mg/kg/day (maximum 300 mg/day) with pyridoxine 10 mg/day and control group receiving placebo. Monitor ALT/AST and SLE disease activity after two weeks, continued monthly for the first three months (1st, 2nd, 3rd) then every three months for up to a year (6th, 9th, 12th months). Routine SLE medication is continued and routinely recorded at every visit.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitas Padjadjaran
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laniyati Hamijoyo, MD, PhD, Principal investigator, Universitas Padjadjaran
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06618573
- Sponsor's protocol ID
- IPD-202402.01
- Status last verified
- Sep 2024
- First submitted
- 19 Sep 2024
- Last updated
- 1 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hamijoyo L, Candrianita S, Rahmadi AR, Dewi S, Darmawan G, Suryajaya BS, Rainy NR, Hidayat II, Moenardi VN, Wachjudi RG. The clinical characteristics of systemic lupus erythematosus patients in Indonesia: a cohort registry from an Indonesia-based tertiary referral hospital. Lupus. 2019 Nov;28(13):1604-1609. doi: 10.1177/0961203319878499. Epub 2019 Sep 29.
PubMed 31566078Koesoemadinata RC, McAllister SM, Soetedjo NNM, Febni Ratnaningsih D, Ruslami R, Kerry S, Verrall AJ, Apriani L, van Crevel R, Alisjahbana B, Hill PC. Latent TB infection and pulmonary TB disease among patients with diabetes mellitus in Bandung, Indonesia. Trans R Soc Trop Med Hyg. 2017 Feb 1;111(2):81-89. doi: 10.1093/trstmh/trx015.
PubMed 28419376Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sanchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG Jr, Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G Jr, Magder LS. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012 Aug;64(8):2677-86. doi: 10.1002/art.34473.
PubMed 22553077Yu YC, Mao YM, Chen CW, Chen JJ, Chen J, Cong WM, Ding Y, Duan ZP, Fu QC, Guo XY, Hu P, Hu XQ, Jia JD, Lai RT, Li DL, Liu YX, Lu LG, Ma SW, Ma X, Nan YM, Ren H, Shen T, Wang H, Wang JY, Wang TL, Wang XJ, Wei L, Xie Q, Xie W, Yang CQ, Yang DL, Yu YY, Zeng MD, Zhang L, Zhao XY, Zhuang H; Drug-induced Liver Injury (DILI) Study Group; Chinese Society of Hepatology (CSH); Chinese Medical Association (CMA). CSH guidelines for the diagnosis and treatment of drug-induced liver injury. Hepatol Int. 2017 May;11(3):221-241. doi: 10.1007/s12072-017-9793-2. Epub 2017 Apr 12.
PubMed 28405790Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997 Sep;40(9):1725. doi: 10.1002/art.1780400928. No abstract available.
PubMed 9324032Victorio-Navarra ST, Dy EE, Arroyo CG, Torralba TP. Tuberculosis among Filipino patients with systemic lupus erythematosus. Semin Arthritis Rheum. 1996 Dec;26(3):628-34. doi: 10.1016/s0049-0172(96)80013-8.
PubMed 8989807Pattanaik SS, Muhammed H, Chatterjee R, Naveen R, Lawrence A, Agarwal V, Misra DP, Gupta L, Misra R, Aggarwal A. In-hospital mortality and its predictors in a cohort of SLE from Northern India. Lupus. 2020 Dec;29(14):1971-1977. doi: 10.1177/0961203320961474. Epub 2020 Sep 30.
PubMed 32998621Lao M, Chen D, Wu X, Chen H, Qiu Q, Yang X, Zhan Z. Active tuberculosis in patients with systemic lupus erythematosus from Southern China: a retrospective study. Clin Rheumatol. 2019 Feb;38(2):535-543. doi: 10.1007/s10067-018-4303-z. Epub 2018 Sep 23.
PubMed 30244432Mok MY, Lo Y, Chan TM, Wong WS, Lau CS. Tuberculosis in systemic lupus erythematosus in an endemic area and the role of isoniazid prophylaxis during corticosteroid therapy. J Rheumatol. 2005 Apr;32(4):609-15.
PubMed 15801014Tam LS, Li EK, Wong SM, Szeto CC. Risk factors and clinical features for tuberculosis among patients with systemic lupus erythematosus in Hong Kong. Scand J Rheumatol. 2002;31(5):296-300. doi: 10.1080/030097402760375205.
PubMed 12455821Ahmmed MF, Islam MN, Ferdous S, Azad AK, Ferdous N. Tuberculosis in Systemic Lupus Erythematosus Patients. Mymensingh Med J. 2019 Oct;28(4):797-807.
PubMed 31599243Jakes RW, Bae SC, Louthrenoo W, Mok CC, Navarra SV, Kwon N. Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: prevalence, incidence, clinical features, and mortality. Arthritis Care Res (Hoboken). 2012 Feb;64(2):159-68. doi: 10.1002/acr.20683.
PubMed 22052624Lisnevskaia L, Murphy G, Isenberg D. Systemic lupus erythematosus. Lancet. 2014 Nov 22;384(9957):1878-1888. doi: 10.1016/S0140-6736(14)60128-8. Epub 2014 May 31.
PubMed 24881804Iliopoulos AG, Tsokos GC. Immunopathogenesis and spectrum of infections in systemic lupus erythematosus. Semin Arthritis Rheum. 1996 Apr;25(5):318-36. doi: 10.1016/s0049-0172(96)80018-7.
PubMed 8778988Yun JE, Lee SW, Kim TH, Jun JB, Jung S, Bae SC, Kim TY, Yoo DH. The incidence and clinical characteristics of Mycobacterium tuberculosis infection among systemic lupus erythematosus and rheumatoid arthritis patients in Korea. Clin Exp Rheumatol. 2002 Mar-Apr;20(2):127-32.
PubMed 12051389
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study on the Safety of Administering Isoniazid to Systemic Lupus Erythematosus Patients to Prevent Tuberculosis
- ClinicalTrials.gov ID
- NCT06618573
- Acronym / sponsor ID
- IPD-202402.01
- Conditions
- Tuberculosis, Systemic Lupus Erythematosus
- Keywords
- Tuberculosis, Systemic Lupus Erythematosus
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Universitas PadjadjaranUniversity, hospital or other
- Study start
- 15 Aug 2022 (actual)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 1 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Systemic Lupus Erythematosus (SLE) is a prototypical systemic autoimmune disease characterized by heterogeneity, multisystem involvement, and production of multiple autoantibodies. Clinical features can vary, from mild skin and joint involvement to severe and life-threatening conditions.
Patients with lupus are more susceptible to infections, in addition to being immunocompromised, and due to the administration of corticosteroid and cytotoxic drugs. The presence of these infections is a cause of death in lupus disease in addition to the activity of the disease itself, especially in Asia-Pacific countries. One infection that often occurs in lupus is Tuberculosis (TB).
Efforts have been made to prevent TB infection in vulnerable populations, including isoniazid (INH) prophylaxis. In 2010, World Heatlh Organization issued guidelines for HIV patients to receive INH prophylaxis to prevent TB infection. The implementation of Isoniazid Preventive Therapy (IPT) is quite cheap using INH with mild side effects.18 A meta-analysis study of INH prophylaxis in patients with HIV found that the efficacy of this prophylaxis significantly reduced TB incidence by 35% with an RR of 0.65%. In addition, INH was found to be safe, with no significant increase in drug reactions, according to a meta-analysis of prophylaxis studies in HIV patients.
However, there is no guideline for INH prophylaxis for SLE patients, as there is for HIV patients, due to lack of data on this issue.
Studies on the effectiveness of INH prophylaxis on the prevention of TB infection for SLE patients should be conducted, but before that, studies on the safety of INH therapy in SLE patients should be conducted.
Detailed description
Systemic Lupus Erythematosus (SLE) is a prototypical systemic autoimmune disease characterized by heterogeneity, multisystem involvement, and production of multiple autoantibodies. Clinical features can vary, from mild skin and joint involvement to severe and life-threatening conditions. The course of lupus is highly variable in the form of relapses and remissions, with mild and severe forms that can be life-threatening. Treatments for SLE includes steroids and immunosuppressants to control disease activity.
Patients with lupus are more susceptible to infections, in addition to being immunocompromised, and due to the administration of corticosteroid and cytotoxic drugs. The presence of these infections is a cause of death in lupus disease in addition to the activity of the disease itself, especially in Asia-Pacific countries. One infection that often occurs in lupus is Tuberculosis (TB).
Tuberculosis is still a problem especially in the Asian region, and Indonesia ranks 2nd with the most cases after India according to World Health Organization in 2019. TB infection is found in 10-11.4% of SLE patients in Asia. The incidence of TB in SLE is reported to range from 150/100,000 patients per year in Turkey to 2,450/100,000 patients per year in India. The annual risk of TB in SLE patients is higher than the normal population. Registry data at Hasan Sadikin Hospital Bandung showed that 11.4% or 93 out of 813 SLE patients were infected with TB after being diagnosed with SLE.
Risk factors for increased TB infection in SLE patients, in addition to SLE disease activity itself (SLEDAI score >12), renal involvement, lymphopenia, and cumulative dose of steroids used by the patient, are also due to long duration of illness and previous history of TB.
Tuberculosis is also one of the infections that cause death in SLE patients. Mortality from TB in Asian countries ranged from 5-31%. A study in the Philippines found that 14.8% of SLE patients with TB died, those who died had disseminated TB or miliary TB.
Efforts have been made to prevent TB infection in vulnerable populations, including isoniazid (INH) prophylaxis. In 2010, World Health Organization issued guidelines for HIV patients to receive INH prophylaxis to prevent TB infection. The implementation of Isoniazid Preventive Therapy (IPT) is quite cheap using INH with mild side effects. A meta-analysis study of INH prophylaxis in patients with HIV found that the efficacy of this prophylaxis significantly reduced TB incidence by 35% with an RR of 0.65%. In addition, INH was found to be safe, with no significant increase in drug reactions, according to a meta-analysis of prophylaxis studies in HIV patients.
The role of isoniazid prophylaxis for TB prevention in patients with SLE is controversial. To date, there is no consensus on prophylaxis against TB in SLE patients.
Research on this prophylaxis has been presented in an Indian study by Gaitonde et al. They found an 82% reduction in TB incidence in SLE patients with prophylactic INH at 5 mg/kg/day, with a maximum dose of 300 mg/day plus 10 mg pyridoxine (Vitamin B6) for 1 year, and no significant liver toxicity due to this drug. However, a retrospective study conducted in Hong Kong found no significant difference in TB reactivation between those who received INH compared to those who did not receive INH, while patients who received INH were reported to have more relapses of their lupus. Similarly, a retrospective study in Korea found no significant difference in patients with lupus nephritis.
The high incidence of TB in SLE patients, especially in endemic areas such as Indonesia, makes TB prevention an important endeavour. However, there is no guideline for INH prophylaxis for SLE patients, as there is for HIV patients, due to lack of data on this issue.
Studies on the effectiveness of INH prophylaxis on the prevention of TB for SLE patients should be conducted, but before that, studies on the safety of INH therapy in SLE patients should be conducted.
This study was a cohort study, with the following research design:
- LES patients attending the rheumatology clinic of RSHS and enrolled as Lupus Registry study participants, with remission or mild SLE disease activity
- Screening for TB and impaired liver function (Informed Consent, history review, physical examination, laboratory examination, Chest X-Ray) -> Exclude if have condition: Impaired liver function, including hepatitis B/C positivity, history of allergy to INH, pregnancy, malignancy
- SLE patients who fulfil the inclusion criteria divided into two groups: Received INH 300 mg/day and Pyridoxine 10 mg/day for nine months or placebo.
- Routine SLE medication continued and routinely recorded at each visit.
- 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 until one year (months 6, 9, 12).
Inclusion Criteria:
- SLE patients with conditions of:
- No signs and symptoms of active TB,
- Not under TB treatment,
- No History of TB, malignancy, HIV, liver function test abnormality
- Not in pregnancy/lactation,
- No other active infections
- Remission or low to moderate disease activity state,
- Consented to join the study completely.
Exclusion Criteria:
- SLE patients with conditions of:
- History of allergy to Isoniazid,
- Chronic liver disease, including chronic hepatitis B or C virus,
- Malignancy,
- Pregnancy.
The patients included were patients who had been diagnosed with SLE and were registered in Lupus Registry.
The study was explained and informed consent was obtained. After the patient agreed and signed Informed Consent, screening was conducted to ensure that there was no active TB, impaired liver function (SGOT/SGPT), positive Hepatitis B (HBsAg) and/or Hepatitis C (total Anti HCV), history of Isoniazid (INH) allergy, history of malignancy, and pregnancy. If any of these conditions exist, the subject will be excluded.
Eligible subjects were randomly grouped into two groups: those receiving INH 5 mg/kg/day (maximum 300 mg/day) \& Pyridoxine (Vitamin B6) 10 mg/day, or placebo. Other routine SLE medications were continued.
Sample calculations were carried out based on INH prophylaxis studies conducted in HIV patients, obtaining a risk of drug reaction events of RR 1.2, so that with a confidence level of 95% and 80% power and an effect size of 0.5, the sample size for each group was 27 people, plus 10% to 30 people. So that the total number of patients involved is 60 people divided into 2 groups.
This study was to assess the safety of INH drug administration to lupus patients assessed by the increase in SGPT and SGOT that occurred and their lupus disease activity (using the SLEDAI score) measured at month 1/2 (second week), 1, 2, 3, 6, 9 and 12. The statistical test used was a T-test comparing two groups.
The study was conducted at Dr. Hasan Sadikin Hospital, Bandung. The study was conducted from August 2022 to December 2024.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- SLE patient at the Hasan Sadikin Rheumatology Outpatient Clinic and registered as Lupus Registry study participants with remission or mild SLE disease activity. Subjects fulfilled inclusion criteria will be randomly divided into two groups: treatment group receiving INH 5 mg/kg/day (maximum 300 mg/day) with pyridoxine 10 mg/day and control group receiving placebo. Monitor ALT/AST and SLE disease activity after two weeks, continued monthly for the first three months (1st, 2nd, 3rd) then every three months for up to a year (6th, 9th, 12th months). Routine SLE medication is continued and routinely recorded at every visit.
| Arm | Type | Receives |
|---|---|---|
| Treatment Group | Active comparator | Drug: Isoniazid/PyridoxineSLE patient at the Hasan Sadikin Rheumatology Outpatient Clinic and registered as Lupus Registry with remission or mild SLE disease activity. The diagnosis of SLE is based on ACR 1997 criteria or SLE SLICC 2012 criteria. Screening will include history review, physical examinations, chest X-Ray, laboratory test such as CBC, ALT/AST, HbsAg, total anti-HCV, complement (C3), dsDNA, creatinine serum, urinalysis (proteinuria, ACR, RBC, WBC, casts), IGRA, to assess if any subject has no active TB and no chronic liver disease. Treatment group receiving Isoniazid 5 mg/kg/day (maximum 300 mg/day) with pyridoxine 10 mg/day. Monitor ALT/AST and SLE disease activity after two weeks, continued monthly for the first three months (1st, 2nd, 3rd) then every three months for up to a year (6th, 9th, 12th months). Routine SLE medication is continued and routinely recorded at every visit. |
| Control Group | Placebo comparator | Drug: Saccharum LactisSLE patient at the Hasan Sadikin Rheumatology Outpatient Clinic and registered as Lupus Registry with remission or mild SLE disease activity. The diagnosis of SLE is based on ACR 1997 criteria or SLE SLICC 2012 criteria. Screening will include history review, physical examinations, chest X-ray, laboratory test such as CBC, ALT/AST, HbsAg, total anti-HCV, complement (C3), dsDNA, creatinine serum, urinalysis (proteinuria, ACR, RBC, WBC, casts) IGRA, to assess if any subject has no active TB and no chronic liver disease. Control group receiving placebo. Monitor ALT/AST and SLE disease activity after two weeks, continued monthly for the first three months (1st, 2nd, 3rd) then every three months for up to a year (6th, 9th, 12th months). Routine SLE medication is continued and routinely recorded at every visit. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- No signs and symptoms of active TB
- Not under TB treatment
- No History of TB, malignancy, HIV, liver function test abnormality
- Not in pregnancy/lactation
- No other active infections
Key exclusion criteria (5 listed)
- History of allergy to Isoniazid
- Chronic liver disease, including chronic hepatitis B or C virus
- Malignancy
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isoniazid/PyridoxineTreatment group received isoniazid 300mg and pyridoxine 10mg/day | Drug | Treatment Group |
| Saccharum LactisAlso: PlaceboControl group received placebo | Drug | Control Group |
Primary outcome
Drug Induce Hepatitis
Time frame: week 2, months 1, 2, 3, 6, 9, 12
Change in more than twice the upper limit of normal SGOT/SGPT values and improvement after drug discontinuation
SLE disease activity
Time frame: month 1, 2, 3, 6, 9, 12
Based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. The higher the score, the worse. SLEDAI score increase in more than 3=flare
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Background: PubMed 31566078Hamijoyo L, Candrianita S, Rahmadi AR, Dewi S, Darmawan G, Suryajaya BS, Rainy NR, Hidayat II, Moenardi VN, Wachjudi RG. The clinical characteristics of systemic lupus erythematosus patients in Indonesia: a cohort registry from an Indonesia-based tertiary referral hospital. Lupus. 2019 Nov;28(13):1604-1609. doi: 10.1177/0961203319878499. Epub 2019 Sep 29.
- Background: PubMed 28419376Koesoemadinata RC, McAllister SM, Soetedjo NNM, Febni Ratnaningsih D, Ruslami R, Kerry S, Verrall AJ, Apriani L, van Crevel R, Alisjahbana B, Hill PC. Latent TB infection and pulmonary TB disease among patients with diabetes mellitus in Bandung, Indonesia. Trans R Soc Trop Med Hyg. 2017 Feb 1;111(2):81-89. doi: 10.1093/trstmh/trx015.
- Background: PubMed 22553077Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sanchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG Jr, Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G Jr, Magder LS. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012 Aug;64(8):2677-86. doi: 10.1002/art.34473.
- Background: PubMed 28405790Yu YC, Mao YM, Chen CW, Chen JJ, Chen J, Cong WM, Ding Y, Duan ZP, Fu QC, Guo XY, Hu P, Hu XQ, Jia JD, Lai RT, Li DL, Liu YX, Lu LG, Ma SW, Ma X, Nan YM, Ren H, Shen T, Wang H, Wang JY, Wang TL, Wang XJ, Wei L, Xie Q, Xie W, Yang CQ, Yang DL, Yu YY, Zeng MD, Zhang L, Zhao XY, Zhuang H; Drug-induced Liver Injury (DILI) Study Group; Chinese Society of Hepatology (CSH); Chinese Medical Association (CMA). CSH guidelines for the diagnosis and treatment of drug-induced liver injury. Hepatol Int. 2017 May;11(3):221-241. doi: 10.1007/s12072-017-9793-2. Epub 2017 Apr 12.
- Background: PubMed 9324032Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997 Sep;40(9):1725. doi: 10.1002/art.1780400928. No abstract available.
- Background: PubMed 8989807Victorio-Navarra ST, Dy EE, Arroyo CG, Torralba TP. Tuberculosis among Filipino patients with systemic lupus erythematosus. Semin Arthritis Rheum. 1996 Dec;26(3):628-34. doi: 10.1016/s0049-0172(96)80013-8.
- Background: PubMed 32998621Pattanaik SS, Muhammed H, Chatterjee R, Naveen R, Lawrence A, Agarwal V, Misra DP, Gupta L, Misra R, Aggarwal A. In-hospital mortality and its predictors in a cohort of SLE from Northern India. Lupus. 2020 Dec;29(14):1971-1977. doi: 10.1177/0961203320961474. Epub 2020 Sep 30.
- Background: PubMed 30244432Lao M, Chen D, Wu X, Chen H, Qiu Q, Yang X, Zhan Z. Active tuberculosis in patients with systemic lupus erythematosus from Southern China: a retrospective study. Clin Rheumatol. 2019 Feb;38(2):535-543. doi: 10.1007/s10067-018-4303-z. Epub 2018 Sep 23.
- Background: PubMed 15801014Mok MY, Lo Y, Chan TM, Wong WS, Lau CS. Tuberculosis in systemic lupus erythematosus in an endemic area and the role of isoniazid prophylaxis during corticosteroid therapy. J Rheumatol. 2005 Apr;32(4):609-15.
- Background: PubMed 12455821Tam LS, Li EK, Wong SM, Szeto CC. Risk factors and clinical features for tuberculosis among patients with systemic lupus erythematosus in Hong Kong. Scand J Rheumatol. 2002;31(5):296-300. doi: 10.1080/030097402760375205.
- Background: PubMed 31599243Ahmmed MF, Islam MN, Ferdous S, Azad AK, Ferdous N. Tuberculosis in Systemic Lupus Erythematosus Patients. Mymensingh Med J. 2019 Oct;28(4):797-807.
- Background: PubMed 22052624Jakes RW, Bae SC, Louthrenoo W, Mok CC, Navarra SV, Kwon N. Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: prevalence, incidence, clinical features, and mortality. Arthritis Care Res (Hoboken). 2012 Feb;64(2):159-68. doi: 10.1002/acr.20683.
- Yazdany J, Dall\'Era M. Definition and classification of lupus and lupus-related disorders. In: Wallace DJ, Hahn BH, editors. DUBOIS\' lupus erythematosus and related syndromes. 8th edition. Philadelphia: Elsevier Saunders; 2013. pp. 1-7.Link provided by the sponsor.
- Global tuberculosis report 2020: executive summary. © World Health Organisation 2020.Link provided by the sponsor.
- Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV- Infected Adults and AdolescentsLink provided by the sponsor.
- Moon JY, Kwon HM, Ahn EY, Park JK, Song YW, Lee EB. Efficacy of Isoniazid Chemoprophylaxis in Lupus Nephritis Patients \[abstract\]. Arthritis Rheumatol. 2015; 67 (suppl 10).(abstract).Link provided by the sponsor.
- National Cancer Institute. Common terminology criteria for adverse events (CTCAE).Link provided by the sponsor.
- Ministry of Health of the Republic of Indonesia. National Guidelines for Medical Services: Tuberculosis Management. Jakarta (2020).Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laniyati Hamijoyo, MD, PhD principal investigator
Universitas Padjadjaran
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Isoniazid/Pyridoxine and Saccharum Lactis in people with Tuberculosis and Systemic Lupus Erythematosus, run by Universitas Padjadjaran at 1 site in Indonesia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Laniyati Hamijoyo, MD, PhD (+62222040151, laniyati.hamijoyo@unpad.ac.id), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Drug Induce Hepatitis (time frame: week 2, months 1, 2, 3, 6, 9, 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06618573, which also lists 25 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024.