E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nutritionally high-risk critically ill mechanically ventilated patients. In this sub-study, eligible and enrolled patients randomized to the high protein dose group will achieve its protein goals by adding high protein PN to EN (combined EN/PN). For patients enrolled to the low dose group, goals can be achieved by EN only. |
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E.1.1.1 | Medical condition in easily understood language |
Critically ill mechanically ventilated adult patients. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 |
To show the effect of providing combined EN/PN to the group prescribed a higher dose (≥2.2 grams/kg/day) of protein/amino acid administration compared to a low group prescribed ≤1.2 gram/kg/day (EN only) on patient’s functional recovery as measured by 6 minute walk distance just prior to hospital discharge. |
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E.2.2 | Secondary objectives of the trial |
- MRC sum-Score at hospital discharge - Hand held dynamometry at hospital discharge - Hand grip dynamometry at hospital discharge - SPPB & FSS-ICU at Hospital discharge - Ultrasound quadriceps at Baseline, ICU discharge and hospital discharge - Questionnaires by telephone survey at 6 months: SF-36, EQ-5D-5L, Katz ADL, Lawton IADL, Employment questionnaire, Living Location and Healthcare resource utilization. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial (EFFORT) |
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E.3 | Principal inclusion criteria |
1. ≥18 years old; 2. Expected to remain mechanically ventilated for an additional 48 hours from screening; 3. And have one or more of the following risk factors that make them at high nutritional risk: a. Low (≤25) or High BMI (≥35) b. Moderate to severe malnutrition (as defined by local assessments). We will document the means by which sites are making this determination and capture the elements of the assessment (history of weight loss, history of reduced oral intake, etc.). c. Frailty (Clinical Frailty Scale 5 or more from proxy) d. Sarcopenia (SARC-F score of 4 or more from proxy) e. From point of screening, projected duration of mechanical ventilation >4 days
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E.4 | Principal exclusion criteria |
1. >96 continuous hours of mechanical ventilation before enrollment 2. Expected death or withdrawal of life-sustaining treatments within 7 days from screening 3. Pregnancy 4. The responsible clinician feels that the patient either needs low or high protein 5. Absolute contraindication to EN 6. Severe metabolic disorders including electrolyte disorders, uncontrolled hyperglycemia, hyperlipidemia, hypophosphatemia. 7. Severe chronic liver disease (MELD-score >20) or acute fulminant hepatitis. 8. Metabolic disorders involving impaired nitrogen utilization 9. Not ambulating independently prior to illness that lead to ICU admission (use of gait aid permitted) 10. Lower extremity injury or impairments that prevents them walking prior to hospital discharge (e.g. amputation, knee/hip injury) 11. Pre-existing cognitive impairment or language barrier that prohibits outcomes assessment 12. Pre-existing primary severe systemic neuromuscular disease resulting in severe weakness pre-ICU (e.g., Guillain Barre) 13. Intracranial or spinal process affecting motor function 14. Patients in hospital >5 days prior to ICU admission
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E.5 End points |
E.5.1 | Primary end point(s) |
Physical Functioning by 6-minute walk test |
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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) |
• Overall strength-upper and lower extremity • Quadriceps force-lower extremity strength • Distal strength-hand grip strength • Overall Physical Functional status • Discharge location (e.g. home vs. rehab) • Body composition via Ultrasound • Body composition via CT (when clinically available) • Health-related quality of life • Physical functioning • Healthcare resource utilization |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Only at Hospital discharge: Overall strength-upper and lower extremity, Quadriceps force-lower extremity strength, Distal strength-hand grip strength, Overall Physical Functional status, Body composition via CT (when clinically available). At Baseline/Screening, ICU discharge & Hospital discharge: Body composition via Ultrasound. Follow Up - Visit at 6 months: Health-related quality of life, Physical functioning, Healthcare resource utilization. |
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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 | Yes |
E.6.4 | Safety | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
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 | No |
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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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |