The Protective Effect for Liver Organ in Patients With Anti-TB Drugs Using of Acetylcysteine (NAC)

the Safety and Effect in TB Patients With NAC

Animal studies have shown that INH-RIF-induced oxidative injury can be prevented by supporting the cellular antioxidant defense mechanism by N-acetylcysteine (NAC). However, there are few published data and large sample sizes regarding the protective effect of NAC against hepatotoxicty induced by anti-TB drugs in humans, to our knowledge.

Therefore, the investigators designed a clinical trial with the aim to see whether NAC could protect against anti-TB drug-induced hepatotoxicity (DIH)

Study Overview

• Status: Unknown
• Conditions: Protective Effect in TB-DIH; TB-DIH Means: Drug Induced Liver Function Abnormalities
• Intervention / Treatment: Drug: Acteylcysteine

Detailed Description

Isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA), the first-line drugs used for tuberculosis (TB) chemotherapy, are associated with hepatotoxicity. A high rate of hepatotoxicity has been reported in some developing countries compared with advanced countries with a similar dose schedule. Sharifzadeh et al. reported an incidence of 27.7% in Iran. The reasons for this higher rate of hepatotoxicity are not completely clear. Ethnic variations, advanced age, female sex, alcoholism, underlying liver disease, acetylator phenotype, hepatitis B and C virus, HIV infection, extensive pulmonary parenchymal disease, and hypoalbuminemia have been observed to be the risk factors for the development of drug-induced hepatotoxicity (DIH) because of anti-TB treatment.

The mechanism of DIH induced by anti-TB treatment is not yet fully understood. Sodhi et al. proposed oxidative stress as one of the likely mechanisms for INH-RIF-induced hepatic injury. It is well established that by augmenting a cellular antioxidative defense system, especially nonprotein thiols, that is, glutathione (GSH), cells can be protected against oxidative injuries produced by various drugs and chemicals.

The study will be performed with randomized trial for assessment and protective effects over liver function in patients receiving anti-TB agents and using NAC.

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 886
    • Far Eastern Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. new diagnosed to have tuberculosis
2. age >20 years -

Exclusion Criteria:

1. acute hepatitis in a previous one year
2. TB drugs induced urticaria or Steven-Johnson syndrome
3. life less than one year due to advanced cancer status
4. non-tuberculosis mycobacteria，NTM patients
5. HIV patients
6. patients can not cooperate
7. Allergic reaction for NAC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAC 1200 mg; patients with add NAC (600) 1# bid use per day during the study period	Drug: Acteylcysteine; randomized into three arms
Experimental: NAC 2400 mg; patients with add NAC (600) 2# bid use per day during the study period	Drug: Acteylcysteine; randomized into three arms
Placebo Comparator: NAC 0 mg; patients with add NAC (600) 0# (placebo) use per day during the study period	Drug: Acteylcysteine; randomized into three arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of DIH	the rate for	during the 6 months treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence for other side effects	side effects including GI upset, blurred vision, neuropathy, renal organ damage	6 months

Collaborators and Investigators

• Sponsor: Far Eastern Memorial Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: August 31, 2016
• First Submitted That Met QC Criteria: September 6, 2016
• First Posted (Estimate): September 7, 2016

Study Record Updates

• Last Update Posted (Estimate): September 13, 2016
• Last Update Submitted That Met QC Criteria: September 9, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: tuberculosis; hepatotoxicity; acetylcysteine
• Additional Relevant MeSH Terms: Congenital Abnormalities
• Other Study ID Numbers: T-6621

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No