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. 2022 Mar 28;50(3):03000605221086457. doi: 10.1177/03000605221086457

Table 1.

Design, intervention (antacid salts), and findings of studies conducted among patients with gastroesophageal reflux disease-related conditions.

Authors Study design Intervention (s) Treatment protocol Results
Johnson and Suralik, 2009 51 Randomized, open-label, crossover study One dose (powder form) of a sodium bicarbonate (2.32 g) and citric acid (2.18 g) combination dissolved in water versus water alone – Interventions were provided at visit 2 or alternatively at visit 3 before breakfast– Doses was separated by a washout period of 36 to 48 hours – Treatment with a sodium bicarbonate and citric acid combination resulted in a statistically significant change in pH from baseline in 6 seconds, compared with 18 seconds for water.
Walker et al., 2015 77 Phase III, randomized study Immediate-release omeprazole plus sodium bicarbonate (one dose [20 mg] per day) versus standard enteric coated omeprazole (one dose [20 mg] per day) – When required, interventions were provided for a period of 3 days during the 14-day study period – Immediate-release omeprazole plus sodium bicarbonate provided significant relief of heartburn associated with GERD within 0 to 30 minutes.
Orbelo et al., 2015 78 Open-label, prospective, randomized clinical trial One sachet in 15 to 30 mL of water per day of an omeprazole and sodium bicarbonate combination – The intervention was provided daily for eight weeks either  • in the morning, i.e., 20 to 60 minutes prior to a meal or  • at night, i.e., immediately prior to sleep – The once-daily dose, taken in the morning or at night, effectively reversed severe reflux esophagitis and improved GERD symptoms.
Higuera-de-la-Tijera, 2018 79 Systematic review of studies published since 2000 Omeprazole and sodium bicarbonate combination versus omeprazole NRa – The combination produced a sustained response and sustained total relief in patients with GERD.
Sulz et al., 2007 80 Open, randomized, placebo-controlled trial Two tablets of a calcium carbonate (680 mg) and magnesium carbonate (80 mg) combination versus magaldrate gel (800 mg) versus placebo – Interventions were provided after an overnight fast of at least 10 hours on 3 different days– The scheduled days were separated by a washout period of 4 days – Both the antacid tablet and gel achieved the target pH (>3.0) during the first 30 minutes.
Collings et al., 2002 81 Single-blind, four-treatment cross-over study Two pellets of calcium carbonate chewing gum (300 mg and 450 mg) versus two chewable tablets of calcium carbonate (500 mg) versus a swallowed placebo capsule – Interventions were provided 30 minutes after a meal in all four sessions – Both gums decreased heartburn for 120 minutes compared with placebo.– The higher gum dose decreased heartburn more strongly than chewable antacids up to 120 minutes.– Antacid gums provided faster and more prolonged symptom relief and pH control than chewable antacids.
Rodriguez-Stanley et al., 2004 82 Prospective clinical study Two chewable tablets of calcium carbonate (1500 mg each) NAb – Calcium carbonate improved the motor function of the esophagus in patients with heartburn, thereby improving acid clearance from the esophagus and into the stomach.
Robinson et al., 2001 83 Randomized, four-way crossover study Ranitidine (75 mg) versus a chewable calcium carbonate (420 mg), ranitidine, and calcium carbonate combination versus placebo – Interventions were provided 1 hour after a meal– Subjects underwent a 7- to 10-day washout period between each treatment – The combination was more effective in reducing meal-induced gastric and esophageal acidity as well as heartburn severity.
Ohning et al., 2000 84 Open, randomized, placebo-controlled trial, four-treatment cross-over study Famotidine (10 mg), calcium carbonate (800 mg), and magnesium hydroxide (165 mg) combination versus ranitidine (75 mg), calcium carbonate (1000 mg) versus placebo – Subjects consumed a peptone meal both 60 and 15 minutes prior to treatment, and then 2.5 and 6 hours after treatment – The combination provided superior control of gastric acidity than either antacids or histamine-type-2 receptor antagonists alone.
Walsh et al., 2000 85 Open (observer-blinded), randomized, placebo-controlled four-period crossover design Famotidine (10 mg), calcium carbonate (800 mg), and magnesium hydroxide (165 mg) combination versus ranitidine (75 mg) and calcium carbonate (1000 mg) combination versus placebo – Subjects consumed peptone meal both 60 and 15 minutes prior to treatment and then 2.5 and 6 hours after treatment – The combination reduced gastric acidity more quickly than ranitidine and continued to control gastric acidity for a longer period than calcium carbonate.
Robinson et al., 2002 86 Randomized, crossover, placebo-controlled study Chewable (750, 1500, or 3000 mg) calcium carbonate tablets versus swallowable (750, 1500, or 3000 mg) calcium carbonate tablets versus placebo – Interventions were provided 60 minutes after dinner– The study period was separated by washout period of at least 24 hours – The onset of action on esophageal pH was similar for all antacids (30–35 minutes). – Chewable tablets and effervescent bicarbonate had relatively long durations of action (esophagus, 40–45 min; stomach, 100–180 min); conversely, swallowable tablets had little effect.
Feldman, 1996 87 Randomized, double-blind, placebo-controlled crossover trial Two calcium carbonate antacid tablets (1000 mg) versus one famotidine tablet (10 mg) – Interventions were provided 60 minutes after the test meal– Two identical meals were consumed 2.5 and 6.0 hours after the medication was given – The onset of action of calcium carbonate was 30 minutes, versus 90 minutes for famotidine. – The duration of action of calcium carbonate was 60 minutes, versus 540 minutes for famotidine.
Netzer et al., 1998 88 Double-blind, placebo-controlled, four-way crossover study Two tablets of a calcium carbonate (680 mg) and magnesium carbonate (80 mg) combination versus one tablet of ranitidine (75 mg) versus one tablet of famotidine (10 mg) versus placebo – Interventions were provided after an overnight fast – The onset of action, for raising pH to >3 was 5.8 minutes for calcium–magnesium carbonate, 64.9 minutes for ranitidine, 70.1 minutes for famotidine, and 240.0 minutes for placebo.– The percentage of time with pH >3.0 was 10.4% for calcium–magnesium carbonate, 61.4% for ranitidine, 56.6% for famotidine, and 1.4% for placebo.
Levine et al., 2004 89 Randomized, double-blind, placebo-controlled, parallel group study Famotidine (10 mg), calcium carbonate (800 mg), and magnesium hydroxide (165 mg) combination (FACT) versus famotidine (10 mg; FAM) versus calcium carbonate (800 mg) and magnesium hydroxide (165 mg) combination versus placebo NAb – Onset of symptom relief was significantly faster with FACT than with FAM (P = 0.001) or placebo (P < 0.001).– Patients with heartburn who received FACT were 1.60- and 2.15-fold more likely to maintain adequate relief at a later time point than those on antacid and placebo, respectively.– The duration of the effect was significantly longer with FACT than with antacid or placebo (P < 0.001).– The proportion of episodes relieved for at least 7 hours was greater with FACT (70.0%) than with antacid (58.5%) or placebo (51.4%).
Decktor et al., 1995 90 Single-blind, three-way crossover design Two chewable tablets of an aluminum hydroxide (800 mg), magnesium hydroxide (800 mg), and simethicone (80 mg) combination (AMH) versus calcium carbonate (1.5 g) – Interventions were provided 60 minutes after dinner – The onset of action was faster with AMH tablets than with calcium carbonate tablets.– The duration of the antacid action of AMH in the esophagus was 82 minutes, versus 60 minutes for calcium carbonate (P < 0.05).–  In the stomach, AMH tablets raised gastric pH significantly compared with placebo (with a duration of action of 26 minutes), but the same was not observed for calcium carbonate.
Parente et al., 1995 91 Double-blind randomized, multicenter study Aluminum phosphate gel (11 g) five times a day versus ranitidine (300 mg) once daily – Interventions were provided for 6 weeks – Ranitidine proved more effective than aluminum phosphate in reducing the frequency and severity of daytime pain attributable to duodenal ulcer.
Weberg and Berstad, 1989 92 Double-blind, randomized, placebo-controlled,crossover trial One chewable antacid tablet (containing 1100 mg of aluminum hydroxide and magnesium carbonate in a co-dried gel) versus a matching placebo – Interventions were provided four times daily– One tablet each was received 60 minutes after the three main meals and one was given at bedtime.– After 2 weeks of treatment, the patients were switched over to the alternative treatment for another 2 weeks– Treatment periods were not separated by any ‘washout interval’ – Antacid treatment provided significant lower global symptomatic scores, less acid regurgitation, and fewer days and nights with heartburn.
Farup et al., 1990 93 Double-blind randomized, placebo-controlled,multicenter study One chewable antacid tablet (containing 1100 mg of aluminum hydroxide and magnesium carbonate in a co-dried gel) four times daily versus one cimetidine (400 mg) tablet twice daily versus a matching placebo – One antacid tablet each was received 60 min after the three main meals and one was given at bedtime for 8 weeks – Both antacids and cimetidine significantly reduced symptoms associated with reflux esophagitis compared with placebo. – During the first and second halves of the study, antacid consumption significantly improved the global assessment score versus cimetidine.
Graham and Patterson, 1983 94 Double-blind, parallel-treatment study 15-mL doses of aluminum hydroxide and magnesium hydroxide combined liquid antacid versus an identical appearing placebo – Interventions were provided seven times daily, i.e., 1 and 3 hours after each meal (three in total) and at bedtime for five weeks – Both the antacid and placebo significantly reduced the severity and frequency of heartburn. – The time to reproduce heartburn was increased by both antacid and placebo therapy.
Meteerattanapipat and Phupong, 2017 95 Randomized double-blind controlled trial 10 mL of alginate-based reflux suppressant (500 mg of sodium alginate, 267 mg of sodium bicarbonate, and 160 mg of calcium carbonate) versus 5 mL of magnesium-aluminum antacid gel (120 mg of magnesium hydroxide and 220 mg of aluminum hydroxide) – Interventions were provided three times after a meal and before bedtime for 2 weeks – No difference in the improvement of heartburn frequency, 50% reduction of the frequency of heartburn, improvement of heartburn intensity, and 50% reduction of heartburn intensity during pregnancy.

aNot relevant because the article was a systematic review of different clinical studies.

bThe data were not available in the published article.