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

NCT03281226 | Unknown Phase 2 DMC

• 1 other identifier: CAAE: 60219916.5.0000.0005
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Tuberculosis, Pulmonary; HIV/AIDS

Keywords

Pulmonary tuberculosis; HIV/AIDS; Glutathione; N-acetylcysteine; Oxidative stress

Outcome Measures

Primary Outcomes (1)

• Number of participants with any biological intolerability or adverse event

  This evaluation will be done by the physician along all the follow-up of the study

  6 months

Secondary Outcomes (3)

• Number of patients in the NAC treatment arm with shorter sputum smear conversion time and culture

  Until week 8

• Number of patients presenting tuberculostatic drug-related hepatotoxicity

  6 months

• Dosage of inflammatory cytokines

  6 months

Study Arms (2)

RIPE (2m) and RI (4m)

ACTIVE COMPARATOR

The patients enrolled in this arm will receive a treatment regimen with an intensive phase lasting two months of rifampicin 150mg + isoniazid 75mg + pyrazinamide 400mg + ethambutol 275mg (combined fixed dose tablet according to the weight) and a continuation with rifampicin 150mg and isoniazid 75mg (combined fixed dose tablet according to the weight) for 4 months.

Drug: RIPE (2m) and RI (4m)

RIPE+NAC (2m) and RI (4m)

EXPERIMENTAL

The patients enrolled in this arm will receive a treatment regimen with an intensive phase lasting two months of rifampicin 150 mg + isoniazid 75 mg + pyrazinamide 400 mg + ethambutol 275mg (combined fixed dose tablet according to the weight) plus N-acetylcysteine (NAC) and a continuation with rifampicin 150mg and isoniazid 75mg (combined fixed dose tablet according to the weight) for 4 months. The NAC is administered by means of effervescent tablet 1200 mg (two sachets of 600 mg) to be diluted in 200ml of water and administered in a 12-hour interval.

Drug: RIPE+NAC (2m) and RI (4m)

Interventions

RIPE (2m) and RI (4m) DRUG

Rifampicin 150mg + isoniazid 75mg + pyrazinamide 400mg + ethambutol 275mg (oral combined fixed dose tablet according to the weight) for 2 months and a continuation with rifampicin 150mg and isoniazid 75mg (oral combined fixed dose tablet according to the weight) for 4 months

RIPE (2m) and RI (4m)

RIPE+NAC (2m) and RI (4m) DRUG

Rifampicin 150 mg + isoniazid 75 mg + pyrazinamide 400 mg + ethambutol 275mg (oral combined fixed dose tablet according to the weight) plus oral N-acetylcysteine (NAC) 1200 mg (600mg twice daily) for 2 months and a continuation with rifampicin 150mg and isoniazid 75mg (oral combined fixed dose tablet according to the weight) for 4 months

RIPE+NAC (2m) and RI (4m)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fundação de Medicina Tropical Dr. Heitor Vieira Dourado: lead

Study Sites (1)

Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

Manaus, Amazonas, 69040000, Brazil

RECRUITING

MeSH Terms

Conditions

Tuberculosis, Pulmonary; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Marcelo C dos Santos, MD, PhD

  Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

  PRINCIPAL INVESTIGATOR

• Bruno B Andrade, MD, PhD

  Fundação Osvaldo Cruz Bahia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Izabella P Safe, MD

CONTACT

(+55 92) 2127 3498; izabellasafe@gmail.com

Marcelo C dos Santos, MD, PhD

CONTACT

(+55 92) 2127 3498; marcelocordeiro.br@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 13, 2017
• Study Start: December 7, 2016
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2019
• Last Updated: February 15, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)