EUROPAC2

Background

Both Hereditary and idiopathic Chronic Pancreatitis present early in childhood, with clearly defined episodes of pancreatic pain. Both conditions have a high risk for the development of complications of pancreatitis and ultimately pancreatic cancer. A targeted, low toxicity treatment administrated early in disease progression is desirable, both to reduce the number of exacerbations and potentially modify disease progressions.

The role of antioxidants in symptom modifications in Hereditary Pancreatitis has not been evaluated by a randomised controlled trial, although a number of studies suggest that they may be beneficial. The usefulness of magnesium therapy has been demonstrated in an animal model of acute pancreatitis. Regardless of whether magnesuim was administrated as a prophylactic or therapeutic infusion it reduced the premature intrapancreatic activation of digestive proteases in the pancreas and had a beneficial effect on the course of experimental pancreatitis.

Study Design

EUROPAC2 is an international, multicentre, randomised, phase III, double blind, placebo controlled, parallel group, outpatient study in patients aged 5-65 with Hereditary Pancreatitis and Idiopathic Chronic Pancreatitis. The trial will recruit 240 patients across three arms; Antox (vers)1.2 plus placebo MGCT, MGCT plus placebo Antox vers(1.2) or Placebo Antox (vers)1.2 plus placebo MGCT. The 9 UK sites will be managed by the LCTU and the continental European sites will be managed by Germany.

Study Objective

The objective of this study is to determine the efficacy of ANTOX (vers)1.2 and MGCT (Magnesiocard®) compared to placebo in the treatment of pain in patients with hereditary pancreatitis and idiopathic chronic pancreatitis

Trial Endpoints

Primary Outcome

• Pancreatic pain, defined as the number of days of typical 'pancreatic' pain during one year, calculated by the number of days recorded with any pancreatic pain

Secondary outcomes

• Intensity of pain recorded using a score (0-10) where 0 is no pain and 10 is the worst pain imaginable.
• Analgesic consumption assessed using 'morphine equivalents'
• The number of days spent in hospital due to painful exacerbations of pancreatitis or due to complications arising due to pancreatitis will be obtained from the patient. The clinician responsible for the care of the patient will independently verify this.
• Quality of Life (QoL) including activities of daily living.
• Inflammatory response and pancreatic activity measured at pre-defined time points assessed by the urinary amylase, the exocrine sufficiency marker, faecal elastase.
• Oxidant stress as measured by urinary thiobarituric acid, at fixed time points.
• Changes in the urinary levels of magnesium, selenium and vitamin C.
• Data acquisition including makers of inflammatory response during acute attack of chronic pancreatitis.

Trial Management

Chief Investigators are Mr Michael G T Raraty, Senior Lecturer and Consultant Surgeon (UK) and Professor Markus M. Lerch, Professor and Chair Department of Gastroenterology, Endocrinology and Nutrition (Continental Europe). The UK sponsor is the Royal Liverpool and Broadgreen University Hospital Trust. Co-sponsor is the University of Liverpool. The UK sites will be centrally co-ordinated by the Liverpool Cancer Trials Unit and any queries should be directed here (please see contact page)

Latest Update

For more information please download the EUROPAC2 information leaflet