Cimetidine on-demand in dyspepsia. Experience with randomized controlled single-subject trials

Area of Science:

• Gastroenterology
• Clinical Pharmacology
• Evidence-Based Medicine

Background:

• Non-ulcer dyspepsia (NUD) symptoms fluctuate, challenging traditional trial validity.
• Previous N-of-1 RCTs suggested cimetidine benefits NUD, but continuous dosing limits interpretation.
• Individualized treatment responses require investigation for optimal therapeutic outcomes.

Purpose of the Study:

• To identify individual responders to cimetidine in NUD, peptic ulcer disease, and oesophagitis.
• To confirm the average beneficial effect of cimetidine across these conditions.
• To evaluate N-of-1 multi-crossover trial designs for on-demand medication assessment.

Main Methods:

• N-of-1 multi-crossover trials comparing on-demand cimetidine (400/800 mg) and placebo.
• Each trial included six cimetidine and six placebo doses, randomized in successive pairs.
• Symptomatic effects measured 1/2-6 hours post-intake, assessed by individual p-values and confidence intervals.

Main Results:

• 52% of NUD patients, 78% with oesophagitis, and 50% with peptic ulcer showed individual p-values < 0.20.
• Clinically significant effects (80% CI) observed in 6 NUD, 3 oesophagitis, and 3 peptic ulcer patients.
• Cimetidine demonstrated significantly greater efficacy than placebo across all three groups (p < 0.0001).

Conclusions:

• Cimetidine taken on-demand can rapidly alleviate dyspeptic symptoms.
• N-of-1 trials are effective in identifying individual responders to cimetidine.
• On-demand cimetidine offers a viable therapeutic option for dyspepsia, peptic ulcer disease, and oesophagitis.