Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06618573
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-09-19
Brief Title:
Safety of Administering Isoniazid to SLE Patients to Prevent TB
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Study on the Safety of Administering Isoniazid to Systemic Lupus Erythematosus Patients to Prevent Tuberculosis
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 effects18 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 065 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
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 effects18 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 065 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 10-114 of SLE patients in Asia The incidence of TB in SLE is reported to range from 150100000 patients per year in Turkey to 2450100000 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 114 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 148 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 065 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 mgkgday with a maximum dose of 300 mgday 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 BC positivity history of allergy to INH pregnancy malignancy
SLE patients who fulfil the inclusion criteria divided into two groups Received INH 300 mgday and Pyridoxine 10 mgday for nine months or placebo
Routine SLE medication continued and routinely recorded at each visit
Monitor SGOTSGPT and SLE disease activity after two weeks continuing monthly in the first three months months 12 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 pregnancylactation
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 SGOTSGPT positive Hepatitis B HBsAg andor 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 mgkgday maximum 300 mgday Pyridoxine Vitamin B6 10 mgday 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 12 so that with a confidence level of 95 and 80 power and an effect size of 05 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 12 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
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 10-114 of SLE patients in Asia The incidence of TB in SLE is reported to range from 150100000 patients per year in Turkey to 2450100000 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 114 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 148 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 065 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 mgkgday with a maximum dose of 300 mgday 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 BC positivity history of allergy to INH pregnancy malignancy
SLE patients who fulfil the inclusion criteria divided into two groups Received INH 300 mgday and Pyridoxine 10 mgday for nine months or placebo
Routine SLE medication continued and routinely recorded at each visit
Monitor SGOTSGPT and SLE disease activity after two weeks continuing monthly in the first three months months 12 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 pregnancylactation
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 SGOTSGPT positive Hepatitis B HBsAg andor 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 mgkgday maximum 300 mgday Pyridoxine Vitamin B6 10 mgday 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 12 so that with a confidence level of 95 and 80 power and an effect size of 05 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 12 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None