E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
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 |
Is there an association between the tonicity of a maintenance solution and fluid retention in subjects fasting for 48 hours? Although one of the most broadly used interventions in hospital medicine, there is an important lack of clinical research on maintenance fluids. The NICE guidelines (Clinical Guideline 174) recommend the use of hypotonic maintenance in adult patients, based on old dietary reference values and on the finding that fluid and sodium overload can lead to increased perioperative morbidity (Lobo et al, Lancet 2002). On the other hand, a debate was started recently on the need to extrapolate pediatric recommendations to adult care, promoting isotonic maintenance solutions to avoid hyponatremia-associated morbidity (Moritz et al, N Engl J Med 2015;373:1350-60 + subsequent letters to the editor). |
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E.2.2 | Secondary objectives of the trial |
Is there an association between the tonicity of a maintenance solution and electrolyte disturbances in subjects fasting for 48 hours? How does the human body handles maintenance fluids with two different tonicities. Effect of both solutions on bioelectrical impedance analysis (total body water, intra- en extracellular water volume) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Normal adults, 18-70 years of age - BMI 17-45 kg/m². - Creatinine clearance >60 ml/min (according to eGFR CKD-EPI formula). |
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E.4 | Principal exclusion criteria |
- Acute medical illness within 3 weeks of first study period - Chronic medication: under diuretic therapy or other chronic medication that interfere with urine output or induce urine retention. All chronic medication should be declared before being enrolled in the study. - Medical history: o cardiac failure, o malnourishment, o diabetes mellitus, o urological disease preventing spontaneous or complete emptying of the bladder, - any medical or non-medical issue preventing complaint-free fasting for 48 hours (e.g. active peptic ulcer, psychosis,…) - obesity with a BMI >45 - Pregnanc |
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E.5 End points |
E.5.1 | Primary end point(s) |
Total urine volume after 48h (after last micturition) (isotonic vs. hypotonic maintenance), measured as area under the urinary output curve |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Urine samples: Subjects void their bladder as the urge rises. Exact timing and volume of diuresis is noted.
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E.5.2 | Secondary end point(s) |
• Fluid balance (after correction for insensible losses) and body weight at 48 hours (isotonic vs. hypotonic maintenance). • Mean sodium and potassium concentration at T48. Extra: description and visualization of urine volume, osmolality and sodium concentration, ADH, aldosterone over the course of 48 hours (isotonic vs. hypotonic maintenance). • Incidence of hyponatremia (< 135 mmol/L), hypokalemia (<3.5 mmol/L) and hypernatremia (> 145 mmol/L) during the study period (isotonic vs. hypotonic maintenance with known potassium content). • Strong ion difference (apparent and effective) and strong ion gap (unbalanced isotonic vs. balanced hypotonic maintenance solutions). • TBW and extracellular volume assessed by bio-impedance analysis at 36/48h (isotonic vs. hypotonic maintenance) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Subjects void their bladder as the urge rises. Exact timing and volume of diuresis is noted. Serum samples at T0-12-24-36-48 Bioelectrical impedance analysis at T0-24-48 Clinical parameters (blood pressure, heart rate, thirst score) at T0-24-48 Body weight at T0-12-24-36-48 |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Description of physiological process |
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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 | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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.8.5 | 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 | 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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At the end of the second of two 48h study periods |
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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 | |