Comparing Acotiamide and Itopride for the Management of Indigestion

A Double-Blind Superiority Randomized Controlled Trial Comparing Acotiamide vs Itopride for Functional Dyspepsia Management

This study is a randomized, double-blinded trial that will compare the effectiveness of two medications, acotiamide and itopride, in treating Functional Dyspepsia. Functional Dyspepsia causes uncomfortable symptoms arising from the gastro-duodenal region, such as fullness after meals, early satiation, stomach pain, and burning.

The primary aim of this trial is to determine whether acotiamide is superior to itopride-specifically by a margin of 15%-at improving these meal-related digestive symptoms.

Participants will be involved in the study for a total of 5 weeks. The study begins with a 7-day baseline period where participants will track their symptoms daily.

Following the baseline period, participants will be randomly assigned to receive either 100mg of acotiamide three times a day or 50mg of itopride three times a day.

The treatment phase will last for 4 weeks, during which participants will take the medication before meals on an empty stomach.

Participants will continue to track their symptoms daily and will complete questionnaires about their overall treatment effect and quality of life at follow-up visits.

Functional Dyspepsia (FD) is defined as gastro-duodenal symptoms occurring without any underlying systemic or metabolic disease, affecting an estimated 8.4% of the global population. Both acotiamide and itopride are established, commercially available medications known to be efficacious in managing FD. However, there is currently no direct comparison between the two drugs to help establish a universally accepted standard of care.

This study is designed as a single-center, randomized, double-blind superiority trial to be conducted at the Aga Khan University Hospital in Karachi, Pakistan. The trial seeks to enroll 368 participants aged 18 to 70 who meet the ROME IV criteria for FD, specifically Postprandial Distress Syndrome (PDS).

Methodology & Procedures:

Baseline Phase: Participants will undergo a 7-day baseline period in which they will discontinue any current gastrointestinal medications to clear residual effects.

Randomization & Blinding: Participants will be randomized via a computer-generated program in a 1:1 ratio to one of two treatment arms. To ensure double-blinding, the hospital pharmacy will encapsulate both acotiamide and itopride into identical opaque capsules, making them indistinguishable in taste, smell, and appearance.

Intervention: The active treatment phase lasts 4 weeks. Group 1 will self-administer 100mg of oral acotiamide thrice daily before meals, while Group 2 will self-administer 50mg of oral itopride thrice daily before meals.

Assessments:

Symptom Severity Diary: Participants will record nine specific symptoms daily on a scale of 0-3 throughout the 5-week study duration.

Overall Treatment Effect (OTE): At week 1 and week 4, participants will evaluate their symptom changes compared to baseline using a 7-point Likert scale.

Quality of Life (QoL): The Short form of NPEAN dyspepsia index (SF-NDI) will be administered at the end of the baseline period (day 7) and at the end of the treatment period (week 4) to assess changes in disease-specific QoL.

Safety Monitoring:

Participants will be monitored for Adverse Events (AE) and Serious Adverse Events (SAE) at the week 1 and week 4 follow-up visits.

All adverse events will be documented in case report forms and tracked by the Principal Investigator until resolution or stabilization, with SAEs being reported to the Ethical Review Committee.

Inclusion Criteria

• Patients experiencing bothersome post-prandial fullness or bothersome early satiation at least three days a week.
• Symptom onset must have occurred six months prior to diagnosis, and symptoms must have been present for at least the past three months.
• No evidence of organic, systemic, or metabolic disease based on clinical investigations and endoscopy.
• Patients with co-existing symptoms of Epigastric Pain Syndrome (EPS) are included only if the symptoms causing the most distress are meal-related.
• Individuals who have already tested negative for H. pylori (separate tests will not be conducted for the study).

Exclusion Criteria

• Patients with an identifiable organic disease that can explain their symptoms, such as peptic ulcer, GERD, or chronic pancreatitis.
• Patients with a history of gastrointestinal surgery.
• History of malignancy in the past five years.
• Patients having major psychiatric or depressive disorders.
• Patients with a history of drug or alcohol abuse.
• Patients with advanced chronic kidney disease.
• Patients with uncontrolled diabetes (HbA1c >8).
• Patients with uncontrolled hypertension.
• Patients diagnosed with Irritable Bowel Syndrome.
• Pregnant or lactating women.
• Patients who have used antibiotics, opioids, or any other medication that -affects gastrointestinal function in the past 4 weeks.
• H. pylori positive patients.
• Patients who cannot fill out scales or record their symptoms.