E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
critical illness requiring mechanical ventilation |
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E.1.1.1 | Medical condition in easily understood language |
patients who are critically ill in the Intensive Care Unit and receiving mechanical ventilation |
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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 |
Does the daily administration of pantoprazole 40mg IV reduce the incidence of clinically important gastrointestinal bleeding in the ICU during patients’ stay in the ICU? |
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E.2.2 | Secondary objectives of the trial |
1. Does the daily administration of pantoprazole 40mg iv reduce the risk of ICU readmission or all-cause mortality over 90 days following randomization?
2. Does the daily administration of pantoprazole 40mg iv reduce the risk of other outcomes, including ventilator associated pneumonia, Clostridium difficile infection and acute kidney injury?
3. Does the daily administration of pantoprazole 40mg iv reduce length of mechanical ventilation during patients’ stay in the ICU, as well as ICU and hospital length of stay and ICU and hospital mortality?
4. Are there any differences in benefits and risks of stress ulcer prophylaxis in critically ill patients with and without COVID-19 infection? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 18 years or more. 2. Receiving invasive mechanical ventilation in an ICU and in the opinion of the treating ICU physician mechanical ventilation will not be discontinued before the end of the day after the next day. 3. Pregnancy excluded in women of child bearing age |
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E.4 | Principal exclusion criteria |
1. The treating clinician considers either Pantoprazole or placebo are indicated or contraindicated for this patient 2. Pantoprazole contraindicated for patient due to local product information 3. Patients in whom a PPI or histamine 2 receptor antagonist (H2RA) is indicated due to active bleeding or increased bleeding risk, defined as patients with acute GI bleeding, severe oesophagitis or peptic ulcer disease within the previous 8 weeks, Zollinger Ellison syndrome, Barrett's oesophagus or any previous admission to hospital because of upper GI bleeding (patients receiving PPIs for mild dyspepsia or mild gastroesophageal reflux disease or an uncertain indication are not excluded) 4. Received invasive mechanical ventilation during this ICU admission for ≥72 hours 5. Patients who have received more than 24 hours treatment (i.e., > one daily dose equivalent) with a PPI or H2RA during this ICU admission 6. Being treated with or need for dual anti-platelet therapy 7. Admitted for palliative care or the ICU physician is not committed to continuing lifesustaining therapies at the time of enrolment 8. Known or suspected pregnancy 9. Clinician, patient, or legal representative declines 10. Previously enrolled in the REVISE trial 11. Enrolled in another trial for which co-enrolment is not approved |
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E.5 End points |
E.5.1 | Primary end point(s) |
proportion of patients diagnosed with clinically important gastroinstestinal bleeding occurring in the ICU or resulting in readmission to the ICU during the index hospital admission censored at 90 days. |
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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) |
i) ventilator associated pneumonia ii) clostridium difficile associated infection iii) new treatment with renal replacement therapy iv) all cause hospital mortality v) ICU readmission within 90 days |
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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 | No |
E.6.5 | Efficacy | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
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 | 1 |
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 | 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 |
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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 has finished when the 4800th participant meets the 90day outcome. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 | 1 |