Safety of Administering Isoniazid to SLE Patients to Prevent TB

NCT06618573 | Recruiting Phase 2 DMC

• 1 other identifier: IPD-202402.01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Tuberculosis; Systemic Lupus Erythematosus

Keywords

Tuberculosis; Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (2)

• Drug Induce Hepatitis

  Change in more than twice the upper limit of normal SGOT/SGPT values and improvement after drug discontinuation

  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

  month 1, 2, 3, 6, 9, 12

Study Arms (2)

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.

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.

Drug: Saccharum Lactis

Interventions

Isoniazid/Pyridoxine DRUG

Treatment group received isoniazid 300mg and pyridoxine 10mg/day

Treatment Group

Saccharum Lactis DRUG

Control group received placebo

Also known as: Placebo

Control Group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• SLE patients with conditions of :
• History of allergy to Isoniazid
• Chronic liver disease, including chronic hepatitis B or C virus
• Malignancy
• Pregnancy

Sponsors & Collaborators

• Universitas Padjadjaran: lead

Study Sites (1)

Rumah Sakit Dr Hasan Sadikin, Universitas Padjadjaran

Bandung, West Java, 40161, Indonesia

RECRUITING

Related Publications (25)

• 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.

  PMID: 31566078 BACKGROUND

• Koesoemadinata 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.

  PMID: 28419376 BACKGROUND

• Petri 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.

  PMID: 22553077 BACKGROUND

• Yu 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.

  PMID: 28405790 BACKGROUND

• Hochberg 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.

  PMID: 9324032 BACKGROUND

• Victorio-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.

  PMID: 8989807 BACKGROUND

• Pattanaik 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.

  PMID: 32998621 BACKGROUND

• Lao 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.

  PMID: 30244432 BACKGROUND

• Mok 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.

  PMID: 15801014 BACKGROUND

• Tam 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.

  PMID: 12455821 BACKGROUND

• Ahmmed MF, Islam MN, Ferdous S, Azad AK, Ferdous N. Tuberculosis in Systemic Lupus Erythematosus Patients. Mymensingh Med J. 2019 Oct;28(4):797-807.

  PMID: 31599243 BACKGROUND

• Jakes 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.

  PMID: 22052624 BACKGROUND

• Lisnevskaia 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.

  PMID: 24881804 BACKGROUND

• Iliopoulos 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.

  PMID: 8778988 BACKGROUND

• Yun 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.

  PMID: 12051389 BACKGROUND

• Erdozain JG, Ruiz-Irastorza G, Egurbide MV, Martinez-Berriotxoa A, Aguirre C. High risk of tuberculosis in systemic lupus erythematosus? Lupus. 2006;15(4):232-5. doi: 10.1191/0961203306lu2289xx.

  PMID: 16686263 BACKGROUND

• Sayarlioglu M, Inanc M, Kamali S, Cefle A, Karaman O, Gul A, Ocal L, Aral O, Konice M. Tuberculosis in Turkish patients with systemic lupus erythematosus: increased frequency of extrapulmonary localization. Lupus. 2004;13(4):274-8. doi: 10.1191/0961203303lu529xx.

  PMID: 15176665 BACKGROUND

• Shyam C, Malaviya AN. Infection-related morbidity in systemic lupus erythematosus: a clinico-epidemiological study from northern India. Rheumatol Int. 1996;16(1):1-3. doi: 10.1007/BF01419946.

  PMID: 8783414 BACKGROUND

• Bharath G, Kumar P, Makkar N, Singla P, Soneja M, Biswas A, Wig N. Mortality in systemic lupus erythematosus at a teaching hospital in India: A 5-year retrospective study. J Family Med Prim Care. 2019 Jul;8(7):2511-2515. doi: 10.4103/jfmpc.jfmpc_362_19.

  PMID: 31463286 BACKGROUND

• Ayele HT, Mourik MS, Debray TP, Bonten MJ. Isoniazid Prophylactic Therapy for the Prevention of Tuberculosis in HIV Infected Adults: A Systematic Review and Meta-Analysis of Randomized Trials. PLoS One. 2015 Nov 9;10(11):e0142290. doi: 10.1371/journal.pone.0142290. eCollection 2015.

  PMID: 26551023 BACKGROUND

• Gaitonde S, Pathan E, Sule A, Mittal G, Joshi VR. Efficacy of isoniazid prophylaxis in patients with systemic lupus erythematosus receiving long term steroid treatment. Ann Rheum Dis. 2002 Mar;61(3):251-3. doi: 10.1136/ard.61.3.251.

  PMID: 11830432 BACKGROUND

• Polachek A, Gladman DD, Su J, Urowitz MB. Defining Low Disease Activity in Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2017 Jul;69(7):997-1003. doi: 10.1002/acr.23109.

  PMID: 27696791 BACKGROUND

• Mikdashi J, Nived O. Measuring disease activity in adults with systemic lupus erythematosus: the challenges of administrative burden and responsiveness to patient concerns in clinical research. Arthritis Res Ther. 2015 Jul 20;17(1):183. doi: 10.1186/s13075-015-0702-6.

  PMID: 26189728 BACKGROUND

• Benichou C. Criteria of drug-induced liver disorders. Report of an international consensus meeting. J Hepatol. 1990 Sep;11(2):272-6. doi: 10.1016/0168-8278(90)90124-a.

  PMID: 2254635 BACKGROUND

• Blakemore R, Story E, Helb D, Kop J, Banada P, Owens MR, Chakravorty S, Jones M, Alland D. Evaluation of the analytical performance of the Xpert MTB/RIF assay. J Clin Microbiol. 2010 Jul;48(7):2495-501. doi: 10.1128/JCM.00128-10. Epub 2010 May 26.

  PMID: 20504986 BACKGROUND

Related Links

• 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.
• Global tuberculosis report 2020: executive summary. © World Health Organisation 2020.
• Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV- Infected Adults and Adolescents
• 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).
• National Cancer Institute. Common terminology criteria for adverse events (CTCAE).
• Ministry of Health of the Republic of Indonesia. National Guidelines for Medical Services: Tuberculosis Management. Jakarta (2020).

MeSH Terms

Conditions

Tuberculosis; Lupus Erythematosus, Systemic

Interventions

Isoniazid; Pyridoxine

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Vitamin B 6; Picolines

Study Officials

• Laniyati Hamijoyo, MD, PhD

  Universitas Padjadjaran

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laniyati Hamijoyo, MD, PhD

CONTACT

+62222040151; laniyati.hamijoyo@unpad.ac.id

Edhyana Sahiratmadja, MD, PhD

CONTACT

+62222040151; e.sahiratmadja@unpad.ac.id

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 19, 2024
• First Posted: October 1, 2024
• Study Start: August 15, 2022
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)