RIPE vs RIPE Plus N-acetylcysteine in Patients With HIV/TB Co-infection

• Status: Unknown status
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Although tuberculosis is a treatable disease, it is currently the infectious disease with the highest mortality in the world. It is estimated that one-third of the world's population is infected. HIV is the main predisposing factor for TB development. The Brazilian Ministry of Health and the World Health Organization recommends that patients should initially be treated orally with RIPE - rifampicin (R), isoniazid (I), pyrazinamide (P) and ethambutol (E). The N-acetylcysteine (NAC) first benefit was reported during the 1960s, when it proved to be an effective mucolytic agent in individuals with cystic fibrosis. Later, a new role arose when investigating its therapeutic potential in acetaminophen intoxication. Cleavage of the acetyl group makes cysteine available for later incorporation into glutathione synthesis, decreased in hepatic injury caused by acetaminophen. This mechanism causes NAC to have an indirect antioxidant effect, which aroused an interest in studying the effect in diseases that occur with oxidative stress. TB and HIV/Aids are also diseases with chronic inflammation. The present study aims to evaluate the effects of NAC as a adjuvant therapy in the treatment of TB. This is a phase II randomized clinical trial in which the safety and tolerability of NAC as adjunctive therapy for TB treatment will be assessed. Fifty-six patients will be randomized into two groups. The first group will receive the standard tuberculosis treatment as recommended by the Brazilian Ministry of Health (RIPE); the second will receive in addition to this treatment 1200mg of NAC per day for two months. In this way, microscopy and culture conversion rate to mycobacteria at 8 weeks, levels of glutathione and biomarkers of immune activation and inflammation in case of TB with or without NAC will be monitored.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
• Treatments: Acetylcysteine; Ethambutol; Isoniazid; N-monoacetylcystine; Pyrazinamide; Rifampin

Criteria

Inclusion Criteria:

• Age greater than or equal to 18 years;

• Acceptance of the HIV test;

• Forecast of hospital stay of more than twenty-four hours;

• Clinical and laboratory indication of RIPE;

• Conditions for puncture of venous access;

Exclusion Criteria:

• Brazilian indigenous people;

• People the refuse to perform HIV test;

• Pregnant women, nursing mothers or pregnant women,

• Extra pulmonary TB, without pulmonary involvement;

• Not be able to perform the collection of sputum or tracheal aspirate for microbiological confirmation;

• No MGIT® positive for Mtb;

• Resistance to Mtb, detected by professional sensitivity;

• Individuals under treatment for bronchospasm secondary to bronchial asthma, according to the decision of the assistant team or researcher of the study;

• Clinical suspicion of gastric or duodenal ulcer, as decided by the assistant team or study investigator; or evidence by upper digestive endoscopy;

• Alanine aminotransferase (ALT) greater than three times normal;

• Need to suspend the RIPE treatment, according to the decision of the assistant team or researcher of the study;

• Lack of adherence to the proposed treatment for more than seven consecutive days.