Table 2.

Characteristics of studies comparing on-demand PPI with placebo.

References	Country	Center (multi, single)	Study design	Inclusion criteria	Exclusion criteria	PPI regimen for continuous therapy	PPI regimen for on-demand therapy	Primary outcome studied	Follow-up period	Esophagitis class
[23]	Sweden & Denmark (25 centers)	Multicenter	Double-blind, randomized, placebo controlled	NERD with resolution of heartburn after short-term treatment (4 to 8 weeks)	Erosive, ulcerative PUD	N/A	Omeprazole 20, omeprazole 10, placebo	Discontinuation of medicine due to unwillingness to continue	6 months	N/A
[24]	65 centers in Denmark, Finland, Norway, and Sweden	Multicenter	Randomized, double-blind, parallel group	Endoscopy-negative GERD treated with 4 weeks of omep 20 or Eso 20	Patients requiring concomitant drugs, NSAIDS, quinidine, etc. excluded	N/A	Esomeprazole 20 mg on demand, placebo on demand	Time to discontinuation of on-demand therapy due to unwillingness to continue	6 months	N/A
[25]	116 centers in the UK, the Republic of Ireland, and Canada	Multicenter	Randomized, double-blind, parallel-group study	Patients with NERD treated with Eso 40, 20, or Omep 20 for 4 weeks	Patients requiring concomitant drugs, NSAIDS, quinidine, etc. excluded	N/A	Esomeprazole 40 mg on demand, esomeprazole 20 mg on demand, placebo on demand	Time to study discontinuation due to unwillingness to continue for any reason	6 months	N/A
[26]	International (Greece, Italy, the Netherlands, Spain, France, Portugal, Sweden, Denmark, Ireland, Belgium, United Kingdom, Russia, Poland, and Lithuania)	Multicenter	Randomized, double-blind, placebo-controlled, withdrawal study	NERD treated with rabeprazole 10 mg PO daily for 4 weeks	Patients with erosive disease and no relief of heartburn in acute 4-week phase	N/A	Rabeprazole 10 mg on demand, placebo on demand	The proportion of patients discontinuing treatment in the on-demand phase because of inadequate heartburn control	6 months	N/A
[27]	Germany 36 centers	Multicenter	Randomized, double-blind, placebo-controlled, parallel-group comparison	Nonerosive GERD or reflux esophagitis grade 1 according to Savary–Miller classification underwent 4 weeks of pantoprazole 20 mg PO OD for 4 weeks	Patients symptomtic after acute phase or nonerosive GERD or reflux esophagitis grade 2 to 4 according to Savary–Miller classification	N/A	Pantoprazole 40 mg on demand, pantoprazole 20 mg on demand, placebo on demand	Discontinuation rate due to insufficient control of heartburn	6 months	Savary-Miller grade 0 or 1
[28]	40 centers in Germany and five in Lithuania	Multicenter	Randomized, double-blind, placebo-controlled parallel-group comparison	Nonerosive GERD or reflux esophagitis grade 1 according to Savary–Miller classification underwent 4 weeks of pantoprazole 20 mg PO OD for 4 weeks	Patients symptomtic after acute phase or nonerosive GERD or reflux esophagitis grades 2 to 4 according to Savary–Miller classification	N/A	Pantoprazole 20 mg on demand, placebo on demand	The number of patients unwilling to continue the therapy and the corresponding reasons for it were analyzed using the Kaplan–Meier analysis	7 months	Savary-Miller grade 0 or 1