Cammarota 2009.

Methods	Aim of study: to test the hypothesis that a mucolytic pretreatment was able to demolish the biofilm architecture, rendering H pylori–resistant strains more vulnerable to antibiotics. Study design: randomised controlled study, open‐label. Study grouping: parallel group. Unit of allocation: by individuals. Country: Italy. Start date: not available in report. End date: not available in report. Duration of participation: 9 weeks. Ethical approval: approved by the ethics committee of Catholic University of Medicine and Surgery.
Participants	Total number randomised: 40. Method of recruitment: consecutive participants who had a history of at least fourH pylori eradication failures, and were therefore referred to a tertiary endoscopy centre for endoscopic examination and H pylori culture. Informed consent obtained: participants provided written informed consent to participate in the study. Baseline imbalances: groups were similar according to age and gender. Withdrawals and exclusions: none. Subgroups measured: none. Subgroups reported: none. Mean age: group A (49 years), group B (47 years). Gender (M/F): group A (8/12), group B (10/10). Race/ethnicity: not available in report. Severity of condition: not available in report. Comorbidities: not available in report. Diagnostic criteria: two gastric biopsy specimens were used for biofilm demonstration by scanning electron microscopy. A biofilm architecture was defined as a dense accumulation of bacteria within an amorphous matrix. Two additional specimens were used for H pylori culture. Setting: tertiary endoscopy centre, single‐centre, outpatients. Inclusion criteria: participants who had a history of at least 4 H pylori eradication failures. Exclusion criteria: participants affected by serious concomitant illnesses and those with recent or continuing use of antibiotics.
Interventions	Number randomised in each group: group A (n = 20), group B (n = 20). Dose Group A: NAC 600 mg once a day for one week, before a culture‐guided 1‐week antibiotic regimen, including a proton pump inhibitor plus two antibiotics. Group B: A culture‐guided 1‐week antibiotic regimen, including a proton pump inhibitor plus two antibiotics. Duration of treatment period: 7 days. Timing: once a day. Delivery: oral. Providers: not reported. Cointerventions: none. Economic information: not available. Resource requirements: not reported. Integrity of delivery: all participants received intervention. Compliance: all participants received intervention.
Outcomes	Primary outcome: eradication rate. Secondary outcomes Side effects Biofilm formation Time points measured and reported Eradication rate: at least two months after the end of therapy, participants underwent urea breath testing to determine their H pylori status. At that time, participants had to discontinue any acid‐suppressive therapy for at least two weeks. Side effects were recorded one week after treatment by a questionnaire. Biofilm formation: participants were invited to repeat endoscopic examination two months after treatment. Outcome definition Eradication rate: number of participants with negative urea breath test after treatment. Side effects: any complaint related to treatment assessed by a questionnaire. Biofilm formation: demonstration by scanning electron microscopy. Person measuring/reporting: not reported. Unit of measurement: % of cure for H pylori eradication. Scales: variable according to outcome. Imputation of missing data: there were no losses. Assumed risk estimates: there were no losses. Power: 80%.
Notes	Publication status: full text. Funding source: the study was funded by the Italian Ministry for University, Scientific, and Technological Research. Conflict of interest: authors declared no conflicts. Contact with authors: we contacted the authors on 26 January 2017 but received no answer.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients were assigned randomly, using a computer‐assisted allocation method". Comment: the authors used an appropriate method for sequence generation.
Allocation concealment (selection bias)	Unclear risk	Comment: insufficient information to allow judgement.
Blinding of participants and personnel (performance bias) Eradication (frequency)	Low risk	Quote: "In an open‐label, randomized controlled trial..."; "...patients underwent urea breath testing to determine their H pylori status". Comment: it is an open label study, but eradication rate was assessed by urea breath test (objective test).
Blinding of participants and personnel (performance bias) Gastrintestinal adverse events	High risk	Quote: "In an open‐label, randomized controlled trial..." Comment: this outcome could be influenced by the lack of blinding.
Blinding of participants and personnel (performance bias) Allergic adverse events	High risk	Quote: "In an open‐label, randomized controlled trial..." Comment: this outcome could be influenced by the lack of blinding.
Blinding of participants and personnel (performance bias) Toxic adverse events	High risk	Quote: "In an open‐label, randomized controlled trial..." Comment: this outcome could be influenced by the lack of blinding.
Blinding of outcome assessment (detection bias) Eradication (frequency)	Low risk	Quote: "In an open‐label, randomized controlled trial...patients underwent urea breath testing to determine their H pylori status" Comment: it is an open label study, but eradication rate was assessed by urea breath test (objective test).
Blinding of outcome assessment (detection bias) Gastrintestinal adverse events	High risk	Quote: "In an open‐label, randomized controlled trial..." Comment: this outcome could be influenced by the lack of blinding.
Blinding of outcome assessment (detection bias) Allergic adverse events	High risk	Quote: "In an open‐label, randomized controlled trial..." Comment: this outcome could be influenced by the lack of blinding.
Blinding of outcome assessment (detection bias) Toxic adverse events	High risk	Quote: "In an open‐label, randomized controlled trial..." Comment: this outcome could be influenced by the lack of blinding.
Incomplete outcome data (attrition bias) Eradication (frequency)	Low risk	No losses
Incomplete outcome data (attrition bias) Gastrintestinal adverse events	Low risk	No losses
Incomplete outcome data (attrition bias) Allergic adverse events	Low risk	No losses
Incomplete outcome data (attrition bias) Toxic adverse events	Low risk	No losses
Selective reporting (reporting bias)	Low risk	All proposed outcomes were properly presented.
Other bias	Low risk	This study seems to be free of other sources of bias.