E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypovolaemia associated with critical illness |
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E.1.1.1 | Medical condition in easily understood language |
The dehydrated state patients can develop when they fall critically ill. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038749 |
E.1.2 | Term | Resuscitation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
Our principle aim is to compare the effects of 5% versus 20% albumin solution when given as fluid resuscitation in critically ill adults. As this is a pilot study, the main objective is to test whether the study processes and procedures are both feasible and safe.
The sorts of effects we will compare include routine observations such as heart rate, blood pressure and the amount of urine a patient produces every hour. We will also compare the biochemical levels of sodium and chloride in patient's blood. The most important comparison we will make is the total amount of fluid (in ml) that patients receive during the study period. |
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E.2.2 | Secondary objectives of the trial |
With regard to the comparison of 5% versus 20% albumin, the research questions we are aiming to answer are as follows:
1. Do patients receiving 20% albumin receive less resuscitation fluid (in ml) compared to those receiving 5% albumin in the first 48 hours following enrolment?
2. Do patients receiving 20% albumin receive a lower overall total volume of fluid (in ml) compared to those receiving 5% albumin in the first 48 hours following enrolment?
3. Does 20% albumin result in higher mean arterial blood pressures compared to 5% albumin during the first 48 hours following enrolment?
4. Does 20% albumin result in lower central venous pressures compared to 5% albumin during the first 48 hours following enrolment?
5. Does the administration of 20% albumin result in lower requirements of medication infusions to maintain normal blood pressure in the first 48 hours following enrolment compared to 5% albumin?
6. Do patients receiving 20% albumin receive less chloride in the first 48 hour |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria:
• Admitted to the intensive care unit for less than 24 hours. • Age 18 years or greater • Need for fluid bolus as determined by the treating clinician • Presence of one or more of the following physiological states: systolic BP <90 mmHg, or MAP <65 mmHg, or increasing need for vasopressor drug infusion or pulse pressure variation >12 % or stroke volume variation >12%, or Cardiac index <2.2 L/min/m2 or heart rate >100 or urinary output <20 ml/hr or either rising lactate levels or lactate levels >2 mmol/L or capillary refill time >3 seconds or central venous pressure <8 mmHg.
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E.4 | Principal exclusion criteria |
Exclusion criteria:
• Confirmed or suspected pregnancy • Patients with traumatic brain injury • Active bleeding • Haemoglobin level <70 g/L • People who refuse blood products • Patients in whom death is considered imminent (within 24 hours)
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E.5 End points |
E.5.1 | Primary end point(s) |
Amount (in ml) of resuscitation fluid administered over the first 48 hours in intensive care. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 48 hours following randomisation. |
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E.5.2 | Secondary end point(s) |
• Secondary efficacy outcomes o The cumulative fluid balance after 48 hours in ICU. o The amount of vasoactive medication given over the first 4 hours after a fluid bolus and over the first 48 hours in ICU. o The total amount of fluids given over the first 4 hours after a fluid bolus, daily and over the first 48 hours in ICU. o The relative change in haemodynamic variables and blood gas results over the first 4 hours after a fluid bolus. o The relative change between baseline and peak creatinine in the first 48 hours after randomization.
• Patient-centred efficacy outcomes o Need for RRT o Renal status at 90 days o Hours on mechanical ventilation o ICU discharge status (alive or dead) o ICU length of stay o Hospital discharge status (alive or dead) o Hospital outcome (discharge destination – home, another hospital, advanced care institution) o Hospital length of stay (date of discharge) o Mortality status at 90 days.
• Feasibility and safety outcomes: o Distribution of values for primary and secondary outcome o Randomized / Screened patients ratio o Data completion rate o Loss to follow-up rate o Recruitment rate and duration o Separation in amount of fluid given
Safety outcomes o Development of side-effects o Episodes of hypotension o Development of kidney failure o Adverse changes in any of the physiological efficacy measures
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Unless otherwise stated above all outcomes will be measured at 48 hours following randomisation. |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Yes |
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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | 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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 1 |