E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylaxis of stress related gastrointestinal bleeding among critically ill patients in the intensive care unit. |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of gastrointestinal bleeding caused by physiological stress among critically ill patients |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022519 |
E.1.2 | Term | Intensive care |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071910 |
E.1.2 | Term | Upper gastrointestinal bleeding |
E.1.2 | System Organ Class | 100000016492 |
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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 |
To assess benefits and harms in the use of pantoprazole as stress ulcer prophylaxis in adult critically ill patients. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Acute admission to the ICU AND • Aged ≥ 18 years AND • One or more of the following risk factors: 1. Shock (continuous infusion with vasopressors or inotropes, systolic blood pressure < 90 mmHg, mean arterial blood pressure < 70 mmHg or lactate > 4 mmol/l) 2. Acute or chronic intermittent or continuous renal replacement therapy 3. Invasive mechanically ventilation which is expected to last > 24 hours. When in doubt of the forecast, the patient should be enrolled. 4. Coagulopathy (platelets < 50 x 109/l or international normalized ratio (INR) > 1.5 or prothrombin time (PT) > 20 seconds) documented within the last 24 hours 5. Ongoing treatment with anticoagulant drugs (prophylaxis doses excluded) 6.History of coagulopathy (platelets < 50 x 109/l or INR > 1.5 or PT > 20 seconds within 6 months prior to hospital admission 7. History of chronic liver disease (portal hypertension, cirrhosis proven by biopsy, computed tomography (CT) scan or ultrasound, history of variceal bleeding or hepatic encephalopathy in the past medical history) |
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E.4 | Principal exclusion criteria |
• Contraindications to PPI • Ongoing treatment with PPI and/or H2RA on a daily basis • GI bleeding of any origin during current hospital admission • Diagnosed with peptic ulcer during current hospital admission • Organ transplant during current hospital admission • Withdrawal from active therapy or brain death • Fertile woman with positive urine human chorionic gonadotropin (hCG) or plasma-hCG • Consent according to national regulations not obtainable |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
90 days post-randomization |
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E.5.2 | Secondary end point(s) |
• Proportion of patients with one or more of the following adverse events: clinically important gastrointestinal bleeding, pneumonia, clostridium difficile infection, or acute myocardial ischemia in the ICU • Proportion of patients with clinically significant GI bleeding in the ICU • Proportion of patients with one or more infectious adverse events (pneumonia or clostridium difficile infection) in the ICU • 1-year “landmark” mortality post-randomization • Days alive without the use of mechanical ventilation, renal replacement therapy or circulatory support in the 90-day period • Number of SARs • A health economic analysis will be performed. The analytic details will be based on the result of the trial and specified (cost-benefit vs cost-minimisation 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 | No |
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 | Yes |
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 | 25 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Denmark |
Finland |
Iceland |
Italy |
Netherlands |
New Zealand |
Norway |
Switzerland |
United Kingdom |
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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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The trial will end when 2 x 1675 (3350) patients has been randomized (July 2017) and 90-days follow-up has been completed (January 2018) |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |