A Phase 2 interventional study of RIPE (2m) and RI (4m) and RIPE+NAC (2m) and RI (4m) in Tuberculosis, Pulmonary and HIV/AIDS, sponsored by Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Status unknown at 1 site in Brazil. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-02-15.
Sponsored by Fundação de Medicina Tropical Dr. Heitor Vieira Dourado · Phase 2, Interventional, and Treatment
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Among 13 studies in Tuberculosis, Pulmonary with a site in Brazil — 2 open to participants now, 2 under way, none of them phase 3. Tuberculosis, Pulmonary · Brazil.
Among the 13 studies in Tuberculosis, Pulmonary with a site in Brazil, this one is the 9th largest by planned enrollment of the 10 interventional ones that give a count, is one of 2 that started in 2016, is one of 5 in phase 2, and was the 6th registered.
319 studies on the registry are indexed under Tuberculosis, Pulmonary; 71 are open to participants now.
Browse Tuberculosis, Pulmonary studies →2 of the 13 studies in Tuberculosis, Pulmonary with a site in Brazil are open now. Recruiting first, the newest first:
Centro Universitário Augusto Motta · Sites in Brazil
Ages 18+
National Institute of Allergy and Infectious Diseases (NIAID) · Sites in Brazil, Argentina, Australia and 13 more countries
Ages 13+
A study can be open while its sites in Brazil have not opened yet or have stopped. Only those recruiting at a site in Brazil →
Of the 46 Tuberculosis, Pulmonary studies recruiting now, 22 (48%) set no upper age limit and 20 (43%) stop at 75 or younger; 11 take children under 18; 7 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
13 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 2 6 · Phase 3 1 · Phase 4 1
First in 2008; this study’s year is marked. 2 started in 2016.
By drug class, each counting the studies that test any of its medicines:
This study's planned enrollment of 50 is below the median of 146 across 227 interventional studies indexed under Tuberculosis, Pulmonary.
Median enrollment 247 across the 10 interventional studies, 801 across the 3 observational. Of the 9 that completed or were terminated, 4 (44%) have results posted.
This tab as a report to print or save as PDF → With an account.
None of the 13 has an industry lead sponsor. The 10 most frequent:
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado is the lead sponsor of 11 studies on the registry; none are open to participants now.
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado has 1 study filed under Tuberculosis, Pulmonary — fewer than ten, so there is no comparison to draw.
None of the studies under way reaches primary completion within a year.
Among the 13 studies in Tuberculosis, Pulmonary with a site in Brazil, from their registry updates:
This tab as a report to print or save as PDF → With an account.
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.
TB and AIDS are also diseases that occur with a chronic inflammatory stimulus, with constant formation of excessive free radicals, leading to cellular and systemic oxidative stress. The effects of NAC in both populations are studied. A study demonstrated that HIV-positive individuals have low levels of glutathione in CD4+ T lymphocytes when compared to healthy controls, these levels being restored after in vivo supplementation with NAC, favoring the production of cytokines involved in Th1 response. They also observed that glutathione depletion in lymphocytes was correlated with increased levels of tumor necrosis factor and free radicals. Some authors suggested that the immune system's inability of HIV-positive individuals (or not) in containing Mycobaterium tuberculosis (Mtb) may be a consequence of low levels of glutathione in macrophages. The same occurred in a model of animals infected with Mtb, suggesting that oxidative stress was partly due to the poor antioxidant defense of the host. NAC supplementation decreases the bacterial load on the spleen and the severity of necrosis in the lung. The balance between oxidative and antioxidant substances plays a critical role in the induction of IL-12 production involved in the Th1 response and suggests that the use of NAC may be useful for better immune control of TB. Additional benefits of NAC in individuals with TB are related to the possible protective effect of hepatic to tuberculostatic drugs and to the direct antimicrobial effect demonstrated in vitro. Some authors suggest that the restoration of glutathione levels reversed the loss of innate immunity functions, pointing to a new mechanism of control of Mtb and a possible complement to antiretroviral treatment. This clinical trial will be undertaken in the Amazonas State (Western Brazilian Amazon), in Manaus, at Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. It is a prospective, open-label, 2-arm, randomized clinical trial. Twenty-five patients will be enrolled in each treatment arm. A total number of 50 patients should be enrolled. Patients hospitalized in the ICU, in the wards or emergency room of the tertiary unit care will be invited to participate in this study. The assessment schedule will be done in days 1, 7, 14, 28, 42, 56, 120 and 180 (in addition, patient will be asked to come back to the health centre if symptoms occurs at any time). Sputum and blood collection and medical evaluation will be performed.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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)
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)
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
Drug page: Acetylcysteine
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
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
Time frame: 6 months
Number of patients in the NAC treatment arm with shorter sputum smear conversion time and culture
This outcome will be monitored by culture of solid (Löwenstein Jensen) and liquid (MGIT) sputum
Time frame: Until week 8
Number of patients presenting tuberculostatic drug-related hepatotoxicity
This outcome will be monitored by hepatic transaminases and bilirubins levels
Time frame: 6 months
Dosage of inflammatory cytokines
This outcome will be evaluate immunological assays in the two groups
Time frame: 6 months
Plan to share: No
No publications or documents are linked to this record.
Started Dec 2016 (actual). Primary completion is estimated for Jun 2019, 30 months after the start.
Of 33 non-industry phase 2 interventional studies under Tuberculosis, Pulmonary, half reached primary completion within 30 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 49. This study's planned 30 months is close to that.
Counting every sponsor, half of 43 studies reached it within 30 months; a quarter within 21 and three quarters within 37.
How these figures are worked out, and which studies are left out of them.
This study is status unknown, as verified in Feb 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Acetylcysteine
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado