E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of symptomatic gallstone disease |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of symptoms due to gallstones |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study is designed to provide evidence regarding the prophylactic use of UDCA in preventing symptomatic gallstone disease after bariatric surgery. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are the assessment of the health care efficiency of prophylactic use of UDCA and its budget impact. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Scheduled to undergo Roux-en-Y gastric bypass or Sleeve Gastrectomy for morbid obesity
• An intact gallbladder
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E.4 | Principal exclusion criteria |
• Symptomatic gallstone disease already present before RYGB or Sleeve Gastrectomy
• Prior bariatric surgery
• Prior gallbladder surgery
• Ascertained or presumptive hypersensitivity to active or excipient ingredients of UDCA.
• Inflammatory bowel disease and other conditions of the small intestine and liver which may interfere with enterohepatic circulation of bile salts (ileal resection and stoma, extra and intra-hepatic cholestasis, severe liver disease)
• Intake of investigational drug within the last 30 days before the screening
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is symptomatic gallstone disease after 24 months, defined as hospital admission or hospital visit for symptomatic gallstone disease.
Hospital visit is a condition, because all patients with noteworthy symptoms will eventually visit the hospital. Mild and self-limiting complaints are not a large burden to the health care system or to the patient, and usually gallstone involvement is not objectified in these patients.
Symptomatic gallstone disease is defined as biliary disease (biliary pancreatitis, acute cholecystitis, choledocholithiasis, cholangitis, or biliairy colics).
Acute pancreatitis is diagnosed when at least two of the three following features are present: 1. Upper abdominal pain; 2. Serum lipase or amylase levels above three times the upper level of normal; 3. Characteristic findings of acute pancreatitis on cross-sectional abdominal imaging. (40) Biliary pancreatitis is diagnosed when one of the following definitions is present 1. Gallstones and/or sludge diagnosed on imaging (transabdominal or endoscopic ultrasound or computed tomography); 2. In the absence of gallstones and/or sludge, a dilated common bile duct on ultrasound (>8 mm in patients ≤75 years old or >10 mm in patients >75 years old); 3. The following laboratory abnormality: alanine aminotransferase (ALT) level >2 times higher than normal values, with ALT >aspartate aminotransferase.
Acute cholecystitis is defined according to the 2007 Tokyo classification. There must be at least one local sign of inflammation: 1. Murphy’s sign; 2. Right upper quadrant mass/pain/tenderness. And at least one systemic sign of inflammation: 1. Fever; 2. Elevated C-reactive protein; 3. Elevated white blood cell count. Positive imaging findings characteristic of acute cholecystitis confirm the diagnosis in case of clinical suspicion.
Biliary colics are defined as upper abdominal pain (either right upper quadrant or epigastric pain) lasting at least 30 minutes with gallstones visible on abdominal imaging, according to the Rome criteria.
Choledocholithiasis is defined as the presence of stones in the extrahepatic bile ducts as proven by clinical imaging OR clinical suspicion based on abnormal liver function tests in combination with upper abdominal pain for which an ERCP or PTC was indicated.
Cholangitis is diagnosed according to the diagnostic criteria of the updated Tokyo Guidelines (TG13). Suspected diagnosis: One item in A + one item in either B or C.
A. Systemic inflammation
A-1. Fever and/or shaking chills (BT >38 °C)
A-2. Laboratory data: evidence of inflammatory response (abnormal white blood cell count, increase of serum C-reactive protein levels, and other changes indicating inflammation)
B. Cholestasis
B-1. Jaundice (T-Bil ≥ 34 μmol/L)
B-2. Laboratory data: abnormal liver function tests (increased serum alkaline phosphatase, gamma-glutamyl transpeptidase, alanine aminotransferase, aspartate aminotransferase levels >1.5x higher than the upper limit of normal value)
C. Imaging
C-1. Biliary dilatation
C-2. Evidence of the etiology on imaging (stricture, stone, stent etc.) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are:
1. The development of gallstones on ultrasound at 24 months in the gallstone negative group.
2. Number of cholecystectomies in the intervention and the placebo group.
3. Side-effects of UDCA.
4. Therapy compliance.
5. Quality of life, cost-effectiveness, cost-utility and budget impact analyses.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of last subject in the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |