Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website https://www.gastrores.org

Original Article

Volume 13, Number 6, December 2020, pages 260-268

Safety and Efficacy of Nitazoxanide-Based Regimen for the Eradication of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis

**Table 1.** Baseline Characteristics of the Included Studies
Authors, year of publication and country	Study design and sample size	Patient population/prior treatments	Eradication regimen	Dose of NTZ and duration	ER and criteria for eradication	Adverse events
HP: Helicobacter pylori; BID: twice a day; TID: three times a day; BS: bismuth subcitrate; LP: lansoprazole; PPI: proton pump inhibitor; GI: gastrointestinal; NTZ: nitazoxanide; RCT: randomized controlled trial; ER: eradication rate.
Megraud et al, 1998, Egypt [16]	Open phase II dose ranging pilot study	Previously untreated dyspeptic patients diagnosed with HP	NTZ + omeprazole 20 mg/day	500 mg BID for 14 days; 500 mg TID for 7 days; or 1,000 mg BID for 7 days.	ER was 65% in 500 BID for 14 days group, 58% in 500 mg TID for 7 days group and 83% in 1 g BID group. Patients were included if HP was positive in two of the following: histology, culture and serology. Same tests were repeated (except for serology) 4 weeks after treatment to confirm eradication. Urea breath test was also performed after treatment.	Minor adverse events were reported in 15 patients.
Sanjurjo et al, 1999, Mexico [25]	Open prospective, longitudinal study	Previously untreated	NTZ + BS + LP 30 mg BID	500 - 1,000 mg in three different regimens	ER was 41.37% in NTZ 1 g + BS 240 mg + PPI for 7 days group, 75% in NTZ 500 + BS 120 mg + PPI for 14 days group and 83% in NTZ 1,000 + BS 240 mg and PPI for 14 days group. Eradication was confirmed with negative urea breath test 6 weeks after treatment.	No serious adverse events were reported.
Campitelli et al, 2008, Argentina [22]	Open label study	Previously untreated	NTZ + LP + amoxicillin for 7 days	500 mg BID	ER was 90%. Eradication was confirmed with negative urea breath test 6 - 8 weeks after treatment.	No major adverse events were reported.
Basu et al, 2008, USA [23]	Open label prospective study	Failed prior treatment regimen	Levofloxacin, esomeprazole, NTZ and doxycycline for 10 days	500 mg BID	ER was 100% in per protocol analysis (90% in intention to treat analysis). Eradication was confirmed with negative stool antigen test in 2 weeks after treatment.	Nausea and bloating were reported in two patients. Non-specific itching was reported in one patient.
Stuppy, 2009, USA [18]	RCS	Previously untreated	Sucralfate + NTZ for 14 days	1,000 mg BID	ER was 73%. Eradication was confirmed with negative salivary HP antibodies 1 to 6 months after the end of therapy.	Yellowing of urine and GI discomfort were reported in few patients
Stuppy, 2010, USA [19]	RCS	39 previously untreated; 11 failed prior treatment	Sucralfate + NTZ for 14 days	1,000 mg BID	ER was 84%. Eradication was confirmed with negative salivary HP antibodies 1 - 6 months after the end of therapy.	Yellowing of urine and GI discomfort were reported in few patients.
Basu et al, 2011, USA [14]	Randomized open label trial	Previously untreated	Levofloxacin, omeprazole, NTZ and doxycycline for 7 days or 10 days	500 mg BID	ER was 93.6% in per protocol analysis (89.4% in intention to treat analysis). Eradication was confirmed with negative stool antigen test in 4 weeks after treatment.	Minor adverse events (headache, abdominal pain, nausea, diarrhea, etc.)
Basu et al, 2013, USA [21]	Randomized open label clinical pilot study	Failed prior treatment regimens	Rifabutin + NTZ + omeprazole + doxycycline (ROAD) or macrodantin + NTZ + doxycycline + omeprazole (MOAD)	500 mg BID	ER was 65.7% overall (72% in ROAD group and 52% in MOAD group).	Minor adverse events like nausea, vomiting, diarrhea and headache.
Ramos-Soriano and Black, 2015, USA [15]	RCS	Previously untreated pediatric population	NTZ for 3 days + azithromycin and cefixime or any third-generation cephalosporin for 7 - 10 days + PPI for 30 days	Mean dose of 327.5 mg BID	ER was 89.2%. Eradication was confirmed with negative urea breath test with resolution of symptoms within 4 months of treatment.	10% patients had minor adverse events like nausea, vomiting and abdominal cramping.
Abd-Elsalam et al, 2016, Egypt [13]	Open label study	Failed clarithromycin-based regimen in the past	Levofloxacin, omeprazole, NTZ and doxycycline for 14 days	500 mg BID	88.3% in per protocol analysis (83% in intention to treat analysis). Eradication was confirmed with negative stool antigen test in 6 weeks after treatment.	Minor adverse events (headache, abdominal pain, nausea, diarrhea, etc.) were noted in 21 patients.
Shehata et al, 2017, Egypt [17]	RCT	Previously untreated patients	Clarithromycin + NTZ and omeprazole for 14 days	500 mg BID	ER was 94.6%. Eradication was confirmed with negative stool antigen test in 6 weeks after treatment.	Abdominal pain, nausea, constipation and dizziness
Waheeb et al, 2018, Egypt [24]	RCT	25 previously untreated patients and 22 patients failed treatment in the past.	Clarithromycin + NTZ + amoxicillin and omeprazole for 14 days	500 mg BID	85% (92% in previously untreated and 77.3% in patients who failed prior treatment). Eradication was confirmed with negative stool antigen test in 6 weeks after treatment.	Minor adverse events like nausea and vomiting were reported in few patients.
Basu et al, 2010, USA [20]	RCT	Previously untreated patients	Levofloxacin, omeprazole, NTZ and doxycycline for 7 days or dexlansoprazole + moxifloxacin + amoxicillin + doxycycline + NTZ for 4 days	500 mg BID	82% eradication in intention to treat analysis. Eradication was confirmed with negative stool antigen test 30 days after treatment.	Minor rash, dizziness, diarrhea and palpitations

Table 1. Baseline Characteristics of the Included Studies

Authors, year of publication and country

Study design and sample size

Patient population/prior treatments

Eradication regimen

Dose of NTZ and duration

ER and criteria for eradication

Adverse events

HP: Helicobacter pylori; BID: twice a day; TID: three times a day; BS: bismuth subcitrate; LP: lansoprazole; PPI: proton pump inhibitor; GI: gastrointestinal; NTZ: nitazoxanide; RCT: randomized controlled trial; ER: eradication rate.

Megraud et al, 1998, Egypt [16]

Open phase II dose ranging pilot study

Previously untreated dyspeptic patients diagnosed with HP

NTZ + omeprazole 20 mg/day

500 mg BID for 14 days; 500 mg TID for 7 days; or 1,000 mg BID for 7 days.

ER was 65% in 500 BID for 14 days group, 58% in 500 mg TID for 7 days group and 83% in 1 g BID group. Patients were included if HP was positive in two of the following: histology, culture and serology. Same tests were repeated (except for serology) 4 weeks after treatment to confirm eradication. Urea breath test was also performed after treatment.

Minor adverse events were reported in 15 patients.

Sanjurjo et al, 1999, Mexico [25]

Open prospective, longitudinal study

Previously untreated

NTZ + BS + LP 30 mg BID

500 - 1,000 mg in three different regimens

ER was 41.37% in NTZ 1 g + BS 240 mg + PPI for 7 days group, 75% in NTZ 500 + BS 120 mg + PPI for 14 days group and 83% in NTZ 1,000 + BS 240 mg and PPI for 14 days group. Eradication was confirmed with negative urea breath test 6 weeks after treatment.

No serious adverse events were reported.

Campitelli et al, 2008, Argentina [22]

Open label study

Previously untreated

NTZ + LP + amoxicillin for 7 days

500 mg BID

ER was 90%. Eradication was confirmed with negative urea breath test 6 - 8 weeks after treatment.

No major adverse events were reported.

Basu et al, 2008, USA [23]

Open label prospective study

Failed prior treatment regimen

Levofloxacin, esomeprazole, NTZ and doxycycline for 10 days

500 mg BID

ER was 100% in per protocol analysis (90% in intention to treat analysis). Eradication was confirmed with negative stool antigen test in 2 weeks after treatment.

Nausea and bloating were reported in two patients. Non-specific itching was reported in one patient.

Stuppy, 2009, USA [18]

RCS

Previously untreated

Sucralfate + NTZ for 14 days

1,000 mg BID

ER was 73%. Eradication was confirmed with negative salivary HP antibodies 1 to 6 months after the end of therapy.

Yellowing of urine and GI discomfort were reported in few patients

Stuppy, 2010, USA [19]

RCS

39 previously untreated; 11 failed prior treatment

Sucralfate + NTZ for 14 days

1,000 mg BID

ER was 84%. Eradication was confirmed with negative salivary HP antibodies 1 - 6 months after the end of therapy.

Yellowing of urine and GI discomfort were reported in few patients.

Basu et al, 2011, USA [14]

Randomized open label trial

Previously untreated

Levofloxacin, omeprazole, NTZ and doxycycline for 7 days or 10 days

500 mg BID

ER was 93.6% in per protocol analysis (89.4% in intention to treat analysis). Eradication was confirmed with negative stool antigen test in 4 weeks after treatment.

Minor adverse events (headache, abdominal pain, nausea, diarrhea, etc.)

Basu et al, 2013, USA [21]

Randomized open label clinical pilot study

Failed prior treatment regimens

Rifabutin + NTZ + omeprazole + doxycycline (ROAD) or macrodantin + NTZ + doxycycline + omeprazole (MOAD)

500 mg BID

ER was 65.7% overall (72% in ROAD group and 52% in MOAD group).

Minor adverse events like nausea, vomiting, diarrhea and headache.

Ramos-Soriano and Black, 2015, USA [15]

RCS

Previously untreated pediatric population

NTZ for 3 days + azithromycin and cefixime or any third-generation cephalosporin for 7 - 10 days + PPI for 30 days

Mean dose of 327.5 mg BID

ER was 89.2%. Eradication was confirmed with negative urea breath test with resolution of symptoms within 4 months of treatment.

10% patients had minor adverse events like nausea, vomiting and abdominal cramping.

Abd-Elsalam et al, 2016, Egypt [13]

Open label study

Failed clarithromycin-based regimen in the past

Levofloxacin, omeprazole, NTZ and doxycycline for 14 days

500 mg BID

88.3% in per protocol analysis (83% in intention to treat analysis). Eradication was confirmed with negative stool antigen test in 6 weeks after treatment.

Minor adverse events (headache, abdominal pain, nausea, diarrhea, etc.) were noted in 21 patients.

Shehata et al, 2017, Egypt [17]

RCT

Previously untreated patients

Clarithromycin + NTZ and omeprazole for 14 days

500 mg BID

ER was 94.6%. Eradication was confirmed with negative stool antigen test in 6 weeks after treatment.

Abdominal pain, nausea, constipation and dizziness

Waheeb et al, 2018, Egypt [24]

RCT

25 previously untreated patients and 22 patients failed treatment in the past.

Clarithromycin + NTZ + amoxicillin and omeprazole for 14 days

500 mg BID

85% (92% in previously untreated and 77.3% in patients who failed prior treatment). Eradication was confirmed with negative stool antigen test in 6 weeks after treatment.

Minor adverse events like nausea and vomiting were reported in few patients.

Basu et al, 2010, USA [20]

RCT

Previously untreated patients

Levofloxacin, omeprazole, NTZ and doxycycline for 7 days or dexlansoprazole + moxifloxacin + amoxicillin + doxycycline + NTZ for 4 days

500 mg BID

82% eradication in intention to treat analysis. Eradication was confirmed with negative stool antigen test 30 days after treatment.

Minor rash, dizziness, diarrhea and palpitations