This study was conducted in treatment-naive adults with drug-susceptible pulmonary tuberculosis in Port-au-Prince, Haiti, to assess the safety, bactericidal activity, and pharmacokinetics of nitazoxanide (NTZ). This was a prospective phase II clinical trial in 30 adults with pulmonary tuberculosis. Twenty participants received 1 g of NTZ orally twice daily for 14 days. A control group of 10 participants received standard therapy over 14 days. The primary outcome was the change in time to culture positivity (TTP) in an automated liquid culture system. The most common adverse events seen in the NTZ group were gastrointestinal complaints and headache. The mean change in TTP in sputum over 14 days in the NTZ group was 3.2 h ± 22.6 h and was not statistically significant (P = 0.56). The mean change in TTP in the standard therapy group was significantly increased, at 134 h ± 45.2 h (P < 0.0001). The mean NTZ MIC for Mycobacterium tuberculosis isolates was 12.3 μg/ml; the mean NTZ maximum concentration (Cmax) in plasma was 10.2 μg/ml. Negligible NTZ levels were measured in sputum. At the doses used, NTZ did not show bactericidal activity against M. tuberculosis Plasma concentrations of NTZ were below the MIC, and its negligible accumulation in pulmonary sites may explain the lack of bactericidal activity. (This study has been registered at ClinicalTrials.gov under identifier NCT02684240.).
Background Effective therapeutics for respiratory viruses are needed. Early data suggest that nitazoxanide (NTZ) may be beneficial for treating acute respiratory viral illness. Methods From March 2014 through March 2017, a double-blind, placebo-controlled trial was conducted in 260 participants ≥1 year old hospitalized with influenza-like illness at 6 hospitals in Mexico. Participants were randomized 1:1 to NTZ (age ≥12 years, 600 mg twice daily; age 4–11 years and 1–3 years, 200 or 100 mg twice daily, respectively) or placebo for 5 days in addition to standard of care. The primary endpoint was time from first dose to hospital discharge. Influenza reverse-transcription polymerase chain reaction and Respifinder 22 multiplex test were used for virus detection. Results Of 260 participants enrolled, 257 were randomized and took at least 1 dose of study treatment (intention-to-treat population): 130 in the NTZ group and 127 in the placebo group. The Kaplan-Meier estimate of the median duration of hospitalization was 6.5 (interquartile range [IQR], 4.0–9.0) days in the NTZ group vs 7.0 (IQR, 4.0–9.0) days in the placebo group (P =.56). Duration of hospitalization between the 2 treatments was similar in children (P =.29) and adults (P =.62), influenza A and B (P =.32), and other respiratory viruses. Seven (5.4%) and 6 (4.7%) participants in the NTZ and placebo groups, respectively, reported serious adverse events. Conclusions Treatment with NTZ did not reduce the duration of hospital stay in severe influenza-like illness. Further analyses based on age and evaluations by virus did not reveal any subgroups that appeared to benefit from NTZ. Clinical Trials Registration NCT02057757.
BACKGROUND: Helicobacter pylori infection has become more and more resistant to conventional first-line treatment regimens. So, there is a considerable interest in evaluating new antibiotic combinations and regimens. Nitazoxanide is an anti-infective drug with demonstrated activity against protozoa and anaerobic bacteria including H. pylori. This work is designed to evaluate the efficacy and safety of a unique triple nitazoxanide-containing regimen as a treatment regimen in Egyptian patients with H. pylori infection.
METHODS: Two hundred and 24 patients with upper gastrointestinal tract (GIT) dyspeptic symptoms in whom H. pylori -induced GIT disease was confirmed were included in the study. They have been randomized to receive either nitazoxanide 500 mg b.i.d., clarithromycin 500 mg b.i.d., and omeprazole 40 mg twice daily for 14 days or metronidazole 500 mg b.i.d., clarithromycin 500 mg b.i.d., and omeprazole 40 mg twice daily for 14 days. Laboratory evaluation for H. pylori antigen within the stool was performed 6 weeks after cessation of H. pylori treatment regimens to assess the response.
RESULTS: The response to treatment was significantly higher in group 1 of nitazoxanide treatment regimen than group 2 of traditional treatment regimen. One hundred and six cases (94.6%) of 112 patients who completed the study in group 1 showed complete cure, while only 63 cases (60.6%) of 104 patients who completed the study in group 2 showed the same response according to per-protocol (PP) analysis (P<.001). The regimen was well tolerated by all the patients enrolled in the study.
CONCLUSION: Nitazoxanide-containing triple therapy is a promising therapy for the first-line eradication of H. pylori. (ClinicalTrials.gov Identifier: NCT02422706).
<b>BACKGROUND: </b>Influenza is an important cause of morbidity and mortality worldwide. Treatment options are scarce, and new drugs with novel mechanisms of action are needed. We aimed to assess the efficacy and safety of nitazoxanide, a thiazolide anti-infective, for treatment of acute uncomplicated influenza.<b>METHODS: </b>We did a double-blind, randomised, placebo-controlled, phase 2b/3 trial in 74 primary care clinics in the USA between Dec 27, 2010, and April 30, 2011. We enrolled participants aged 12-65 years with fever, at least one respiratory symptom, and one constitutional symptom of influenza within 48 h of symptom onset. We randomly assigned participants to receive either nitazoxanide 600 mg, nitazoxanide 300 mg, or placebo twice daily for 5 days, (ratio 1:1:1) and followed them up for 28 days. Randomisation lists were computer generated and done in blocks of three. Sponsor, investigators, study monitors, patients, and laboratory personnel were all masked to treatment allocation in the study. The primary endpoint was the time from first dose to alleviation of symptoms. The primary analysis was by intention-to-treat for participants with influenza infection confirmed by RT-PCR or culture at baseline. This trial is registered with ClinicalTrials.gov, number NCT01227421.<b>FINDINGS: </b>Of 650 participants screened, 624 (96%) were enrolled. Of these, 212 were randomly assigned to receive placebo twice a day, 201 to receive nitazoxanide 300 mg twice a day, and 211 to receive nitazoxanide 600 mg a day. The median duration of symptoms for participants receiving placebo was 116·7 h (95% CI 108·1-122·1) compared with 95·5 h (84·0-108·0; p=0·0084) for those receiving 600 mg nitazoxanide and 109·1 h (96·1-129·5, p=0·52) for those receiving 300 mg nitazoxanide. Adverse events were similar between the three groups, the most common being headache reported by 24 (11%) of 212 patients enrolled in placebo group, 12 (6%) of 201 patients in the low-dose group, and 17 (8%) of 211 patients in the high-dose group, or diarrhoea, reported by seven (3%) patients in the placebo group, four (2%) patients enrolled in the low-dose group, and 17 (8%) patients in the high-dose group.<b>INTERPRETATION: </b>Treatment with nitazoxanide 600 mg twice daily for 5 days was associated with a reduction of the duration of symptoms in participants with acute uncomplicated influenza. Further studies are warranted to confirm these findings and to assess efficacy of the drug alone or in combination with existing drugs in seriously ill patients and those at risk of influenza complications.<b>Funding: </b>Romark Laboratories LC.
<b>OBJECTIVE: </b>To see the efficacy and safety of 250 mg of Saccharomyces boulardii twice daily for 5 d in acute childhood diarrhea.<b>METHODS: </b>Children aged between 3 mo and 59 mo with acute onset diarrhea (of less than 48 h) admitted in DTTU (diarrhea treatment and training unit) were included and those with clinical evidence of severe malnutrition, systemic infection, encephalopathy and/or convulsion, electrolyte imbalance, invasive diarrhea or previous use of any probiotics were excluded from the study. Those included randomly were given either a placebo or Saccharomyces boullardi (SB) in identical packets mixed with puffed rice powder.<b>RESULTS: </b>Mean post intervention duration of diarrhea was significantly (95% CI = -28.13 to -5.43) shorter in SB group (52.08 ± 24.57 h) as compared to placebo group (64.04 ± 30.43 h). The time of appearance of first semi formed stool in SB group (39.48 ± 23.09 h) was significantly (95% CI -25.4 to -3.87) shorter than the placebo group (54.13 ± 28.21 h). No statistically significant difference was found in rest of the parameters.<b>CONCLUSIONS: </b>There is initial evidence available that SB may have a therapeutic role in the management of acute childhood diarrhea.
BACKGROUND: The aim of the present study was to evaluate the effectiveness of zinc, probiotic bacteria, and lactose-free formula and their different combinations in the treatment of rotavirus diarrhea in young children.
METHODS: Eight different treatment groups were formed: group 1, 60 patients receiving Saccharomyces boulardii; group 2, 60 patients receiving zinc; group 3, 60 patients receiving lactose-free formula; group 4, 60 patients receiving S. boulardii plus zinc; group 5, 60 patients receiving S. boulardii plus lactose-free formula; group 6, 60 patients receiving zinc plus lactose-free formula; group 7, 60 patients receiving S. boulardii plus zinc plus lactose-free formula; group 8, 60 patients receiving only oral and/or parenteral rehydration solutions.
RESULTS: No statistically significant differences were found in the time to resolution of fever after intervention between the treatment groups and the control group. The time to resolution of vomiting was significantly lower in group 4 compared with groups 1 and 5. The duration of diarrhea was significantly reduced in groups 2 and 4 compared to control. A statistically significant difference in the duration of hospitalization was observed for the groups 2 and 4 in comparison to the control group.
CONCLUSIONS: A different combination of adjunct therapies did not seem to bring additional value to rehydration therapy in children with rotavirus diarrhea except for in those receiving only zinc and zinc plus S. boulardii. Further studies are required to determine the optimal protocol of adjunct therapy use in children with rotavirus diarrhea.
OBJECTIVE: The aim of the study was to determine whether an oral treatment with a commercial pharmaceutical product containing Saccharomyces boulardii would reduce the duration of diarrhea in infants with acute diarrhea.
PATIENTS AND METHODS: In the present double-blind, placebo-controlled study, 186 infants, 6 to 48 months old and hospitalized within 72 hours after the onset of acute diarrhea in 2 hospitals in Goiânia, Goiás, Brazil, were randomly assigned to receive twice per day for 5 days 200 mg of a commercial pharmaceutical product containing 4 × 10 viable cells of S boulardii or a placebo. Stool samples were submitted to search for rotavirus. Among the 176 infants who completed the trial, those treated with S boulardii (90) showed a reduction in diarrhea duration (P < 0.05) when compared with the placebo group (86).
RESULTS: The present study shows a reduction in diarrhea duration when S boulardii was given to children within 72 hours after the onset of acute diarrhea.
CONCLUSIONS: The present study suggests a complementary treatment of acute diarrhea in infants with daily oral doses of S boulardii.
<b>BACKGROUND: </b>Evidence suggests that probiotics reduce rotavirus diarrhoea duration. Although there are several probiotic strains potentially useful, daily practice is often limited by the type and number of products locally available. In general, information about combined products is scarce. In this study we compare the effect of two probiotic products in the treatment of diarrhoea in children less than 2 years of age.<b>METHODS: </b>A Randomized double-blind controlled clinical trial in children hospitalized for acute rotavirus diarrhoea, in the Paediatric Centre Albina Patino, Cochabamba, Bolivia.Participants were children aged 1 - 23 months, who were randomly assigned to receive one of three treatments: Oral rehydration therapy plus placebo; Oral rehydration solution plus Saccharomyces boulardii; or Oral rehydration solution plus a compound containing Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium longum and Saccharomyces boulardii. Sample size was 20 per group and the outcomes were duration of diarrhoea, of fever, of vomiting and of hospitalization.<b>RESULTS: </b>64 cases finished the protocol. On admission, patients' characteristics were similar. Median duration of diarrhoea (p = 0.04) in children who received the single species product (58 hours) was shorter than in controls (84.5 hrs). Comparing children that received the single probiotic product and controls showed shorter duration of fever (18 vs 67 hrs) (p = 0.0042) and the mixed probiotic of vomiting (0 vs 42.5 hrs) (p = 0.041). There was no effect on duration of hospitalization (p = 0.31). When experimental groups were merged, statistical significance of changes increased (total duration of diarrhoea, fever and vomiting P = 0.025, P = 0.025 and P = 0.014, respectively).<b>CONCLUSIONS: </b>Both products decreased the duration of diarrhoea compared to oral rehydration solution alone. This decrease was significant only for the single species product which also decreased the duration of fever. With the multiple species product there was no vomiting subsequent to the initiation of treatment. The quantity of probiotic bacteria needed for optimum treatment of gastroenteritis remains to be determined, particularly when multiple species are included in the product.Trial registration: ClinicalTrials.gov ID: NCT00981877Link: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol/sid/S0002653/selectaction/View/ts/2/uid/U0000N04<b>Trial Registration: </b>Clinical trials NCT ID: NCT00981877.
This is a randomized clinical trial designed to evaluate oral nitazoxanide compared to a placebo in the treatment of acute uncomplicated influenza in adults. We hypothesize that treatment with nitazoxanide will reduce the duration of symptoms in patients with confirmed influenza infection. Secondarily, we hypothesize that treatment with nitazoxanide will reduce the complications of influenza, severity of symptoms, time lost from work, time to return to normal daily activities, and viral shedding.
This study was conducted in treatment-naive adults with drug-susceptible pulmonary tuberculosis in Port-au-Prince, Haiti, to assess the safety, bactericidal activity, and pharmacokinetics of nitazoxanide (NTZ). This was a prospective phase II clinical trial in 30 adults with pulmonary tuberculosis. Twenty participants received 1 g of NTZ orally twice daily for 14 days. A control group of 10 participants received standard therapy over 14 days. The primary outcome was the change in time to culture positivity (TTP) in an automated liquid culture system. The most common adverse events seen in the NTZ group were gastrointestinal complaints and headache. The mean change in TTP in sputum over 14 days in the NTZ group was 3.2 h ± 22.6 h and was not statistically significant (P = 0.56). The mean change in TTP in the standard therapy group was significantly increased, at 134 h ± 45.2 h (P < 0.0001). The mean NTZ MIC for Mycobacterium tuberculosis isolates was 12.3 μg/ml; the mean NTZ maximum concentration (Cmax) in plasma was 10.2 μg/ml. Negligible NTZ levels were measured in sputum. At the doses used, NTZ did not show bactericidal activity against M. tuberculosis Plasma concentrations of NTZ were below the MIC, and its negligible accumulation in pulmonary sites may explain the lack of bactericidal activity. (This study has been registered at ClinicalTrials.gov under identifier NCT02684240.).
