Evaluation of Metamizole Sodium Monohydrate for Pain Management in Patients with Chronic Pancreatitis: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to evaluate the efficacy of **metamizole** in reducing pain in patients with **chronic pancreatitis**. Specifically, the study aims to determine if the addition of metamizole, administered three times daily at a dosage of 1000 mg, to the existing analgesic regimen can effectively alleviate pain in patients diagnosed with chronic pancreatitis within the last three years. This is clinically relevant as chronic pancreatitis is a debilitating condition characterized by persistent pain, and optimizing pain management strategies is crucial for improving patient quality of life. No secondary objectives are specified for this study.

The clinical trial focuses on individuals diagnosed with **chronic pancreatitis**, specifically those experiencing abdominal pain typical of the condition, characterized by dull epigastric pain with a Numeric Rating Scale (NRS) score of 3 or higher, occurring at least three days per week for two weeks. The study population includes both male and female participants, with age categories ranging from 18 to 64 years. Participants are not drawn from a vulnerable population. The sponsor has not provided information regarding the total number of participants. The trial population was selected based on confirmed diagnoses of chronic pancreatitis and specific pain criteria. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **metamizole sodium monohydrate** as a pain treatment in patients with **chronic pancreatitis**. This is a multicenter, randomized, double-blind, placebo-controlled trial. The trial aims to determine if adding metamizole at a dosage of 1000 mg three times daily to the current analgesic therapy can effectively reduce pain in patients diagnosed with chronic pancreatitis for less than three years. The trial is expected to commence on May 2, 2024, and conclude by July 1, 2025, with recruitment starting on December 1, 2023.

Participants will be randomly assigned to receive either the active treatment, Dolamizol 500 mg tablet, or a placebo, both administered orally. The study will include several key visits: an initial screening visit to confirm eligibility based on criteria such as confirmed chronic pancreatitis and typical abdominal pain, followed by regular follow-up visits to monitor pain intensity and any side effects. The primary endpoint is the mean daily pain intensity score recorded over a four-week intervention period using an 11-point numerical rating scale. Secondary endpoints include the Izbicki pain score, quality of life assessments, and patient satisfaction.

The expected duration of participant involvement is approximately 14 months, from the screening phase through to the end-of-study visit. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse reactions to the study medication, or withdrawal of consent by the participant. The trial is categorized as a Phase IV trial, indicating it is conducted after the drug has been marketed to gather additional information on the drug's effect in a larger population.

The clinical trial involves the administration of **Dolamizol**, a 500 mg tablet containing the active substance **metamizole sodium monohydrate**. This pharmaceutical form is a tablet, and the route of administration is oral. Participants will receive a dosage of 1000 mg three times daily, with a maximum daily dose of 4000 mg. The treatment period is limited to a maximum of two days. The tablet is characterized by a water-soluble, pH-independent film coating, ensuring consistent drug release and absorption. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

In addition to the experimental treatment, a **placebo** is used as a comparator in this double-blind, placebo-controlled trial. The placebo is a film-coated tablet designed to mimic the appearance of the Dolamizol tablet, containing no active substance. It is administered orally at the same frequency and dosage as the experimental medication, ensuring blinding of both participants and investigators. The use of a placebo allows for the assessment of the true efficacy of metamizole sodium monohydrate in reducing pain in patients with chronic pancreatitis.

Efficacy in the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the mean daily pain intensity score, which will be recorded by patients during the 4-week intervention period using an 11-point numerical rating scale, where 0 indicates no pain and 10 represents the worst pain imaginable. This self-reported measure will provide a direct assessment of pain reduction in patients with chronic pancreatitis.

Secondary endpoints include a variety of measures to further evaluate the efficacy of the treatment. These include the Izbicki pain score, COMPAT-SF, the mean of maximum daily pain intensity scores, the number of patients achieving successful pain reduction, the number of pain-free days, and the number of days with acceptable pain levels. Additionally, the total amount of milligrams of morphine equivalent (MME) and MME required as escape medication will be recorded. Quality of life will be assessed using PANQOLI and SF-36 scales, while patient satisfaction will be measured with the Patient Global Impression of Change (PGIC). Side effects will also be monitored as part of the secondary endpoints.