A total of 82 studies (31 papers and 51 abstracts) involving 110 treatment arms (6123 patients) were included.
Results from the intention-to-treat analysis are reported.
Proton pump inhibitor, clarithromycin and amoxycillin (PAC combination).
Proton pump inhibitor, clarithromycin and metronidazole (PMC combination) given for seven days.
PAC combination (proton pump inhibitor, clarithromycin and amoxycillin).
Overall pooled eradication rate was 84.6% (95% CI: 81.6%, 87.7%).
Dose of clarithromycin (39 treatment arms with 2455 patients for clarithromycin 500 mg and 16 treatment arms with 766 patients for clarithromycin 250 mg): Pooled eradication rates were significantly higher with clarithromycin 500 mg compared to clarithromycin 250 mg (86.6% versus 78.2%; P < 0.0001). Head to head comparative trials gave similar results (4 trials with 192 patients for clarithromycin 500 mg and 4 trials with 193 patients for clarithromycin 250 mg): eradication rates 89.6% for 500 mg dose versus 79.8% for 250 mg dose.
Dosing frequency of proton pump inhibitor (PPI) with clarithromycin 250 mg (11 treatment arms with 571 patients for PPI b.d. and 5 treatment arms with 195 patients for PPI): Pooled eradication rates were significantly higher with PPI twice daily compared to PPI once daily (81.1% versus 69.7%; P <= 0.001).
PMC combination (proton pump inhibitor, clarithromycin and metronidazole).
Overall pooled eradication rate was 87.2% (95% CI: 84.8%, 89.5%).
Dose of clarithromycin (15 treatment arms with 836 patients for clarithromycin 500 mg and 40 treatment arms with 2057 patients for clarithromycin 250 mg): No significant difference in eradication rates with clarithromycin dose (86.7% versus 88.3%). Head to head comparative trials also showed no significant difference (4 trials with 324 patients for clarithromycin 500 mg and 4 trials with 318 patients for clarithromycin 250 mg): eradication rates 88.9% for 500 mg dose versus 87.4% for 250 mg dose (P = 0.6503).
Dosing frequency of proton pump inhibitor (PPI) with clarithromycin 250 mg (13 treatment arms with 585 patients for PPI twice daily and 27 treatment arms with 1472 patients for PPI once daily): Pooled eradication rates were significantly higher with PPI twice daily compared to PPI once daily (88.7% versus 81.7%; P <= 0.001).
Study design.
There was no significant difference in eradication rates between RCTs and cohort or open trials with respect to clarithromycin dose and frequency of dosing for PMC or PAC combination therapy.
Adverse events.
Treatment related drop-outs (58 studies with 69 treatment arms and 4266 patients) and adverse events (49 studies with 55 treatment arms and 3469 patients):
PAC combination (proton pump inhibitor, clarithromycin and metronidazole): 33.7% reported adverse events and 1.2% dropped out. Significantly more patients on clarithromycin 500 mg compared clarithromycin 250 mg experienced adverse events (39.7% versus 30%; P < 0.0001) though no significant difference in drop-outs (1.7% versus 1%; P = 0.3356).
PAC combination (proton pump inhibitor, clarithromycin and amoxycillin): significantly lower rates of adverse reactions than in PMC group (21.4% versus 33.7%; P < 0.0001). Drop-out rates were similar to those of the PMC group (1.8% versus 1.2%; P = 0.1264). No significant differences were found in either adverse event rates according to clarithromycin dose.