E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypovolaemia due to acute blood loss in elective abdominal surgery |
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E.1.1.1 | Medical condition in easily understood language |
Decreased blood volume due to acute blood loss during scheduled surgery of the abdomen |
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E.1.1.2 | Therapeutic area | Diseases [C] - Injuries, poisonings, and occupational diseases [C21] |
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 | 10021137 |
E.1.2 | Term | Hypovolaemia |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
Investigate the safety and efficacy of a 6% HES 130 versus an electrolyte solution in patients undergoing elective abdominal surgery |
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E.2.2 | Secondary objectives of the trial |
Further investigation of safety and efficacy of the applied products |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female adult patients > 40 and ≤85 years of age Women of childbearing potential must test negative on standard pregnancy test (urine or serum) Patients undergoing elective abdominal surgery with an expected blood loss of ≥ 500 ml ASA Physical Status II-III Signed written consent form |
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E.4 | Principal exclusion criteria |
Hypersensitivity to the active substances or to any of the other excipients of the investigational products Body weight ≥ 140 kg Sepsis Burns Renal impairment (AKIN stage ≥ 1 or chronic) or acute and/or chronic renal replacement therapy Intracranial or cerebral haemorrhage Critically ill patients (typically admitted to the intensive care unit) Dehydration Hyperhydration Pulmonary oedema Congestive heart failure Severe hypernatraemia Severe hyperchloraemia Hyperkalaemia Metabolic alkalosis Severely impaired hepatic function Severe coagulopathy Organ transplant patients Simultaneous participation in another interventional trial (drugs or medical device) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in mean estimated glomerular filtration rate (eGFR) between the two treatment groups, calculated from the highest Cystatin-C level measured during post-operative days (POD) 1-3. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Cystatin-C levels will be determined on POD 1-3. eGFR will be calculated from the highest Cystain-C level during this period. |
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E.5.2 | Secondary end point(s) |
Safety - Renal function: Cystatin-C, serum creatinine (SCr), Cystatin-C based estimated glomerular filtration rate (eGFR), Cystatin-C based mean eGFR, SCr based eGFR, AKIN score, RIFLE score, unrine output (if available) - Coagulation: Platelet count, International norm ration (INR), activated partial thromboplastin time (aPTT) - Inflammation: C-reactive protein (C-RP) - Adverse events: (serious) adverse events ((S)AEs / reactions ((S)ARs) - Calculated red blood cell (RBC) loss - Estimated intra-operative blood loss - Outcome: Length of stay (LOS) in the hospital (LOS-H), LOS in the intensive care unit (LOS-ICU; if applicable), fit for discharge from ICU / hospital, hours on mechanical ventilation (MV), mortality (in hospital/out of hospital) and its cause, days on RRT, (new) renal replacement therapy (RRT)
Efficacy - Fluid administration: administration of IP volume - Fluid balance: fluid input and output - Haemodynamics / vital signs: temperature (T), heart rate (HR), mean arterial pressure (MAP), systolic arterial blood pressure (SAP), diastolic arterial blood pressure (DAP), central venous pressure (CVP, if available) - At least one of the following parameters to evaluate responsiveness and guide administration (vol guide): stroke volume (SV), stroke volume variation (SVV), stroke volume index (SVI), pulse pressure variation (PPV) Arterial Blood Gas Analysis (ABGA): partial pressure of carbondioxide (pCO2), partial pressure of oxygen (pO2), hydrogen carbonate (HCO3-), arterial oxygen saturation (SaO2), haemoglobin (Hb), haematocrit (Hct), pH, base excess (BE), lactate centralvenous oxygen saturation (ScvO2) (if available) Serum electrolytes (S elyte): Sodium, potassium, calcium, chloride Major post-operative complications
Definition of time-points Screening (Within 1 week before surgery) T0 (Baseline; after randomization and prior induction of anaesthesia) T1 (during surgery) T2 (end of surgery) T3 (POD 1 morning) T4 (POD 2-3 morning) T5 (POD 4-7 morning or hospital discharge whatever occurs first) T6 (POD 8-10 morning or hospital discharge whatever occurs first) T7 ( POD 28) ± 5 days T8 (POD 90) ± 19 days T9 (1 year PO) ± 30 days |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Cystatin-C: T0, T2-T8 SCr: T0, T2, T3, T4, T7, T8 Cystatin-C-based eGFR: T0, T2, T3, T4, T7, T8 Cystatin-C-based mean eGFR: T3-T6 SCr-based eGFR: T0, T2, T3, T4, T7, T8 AKIN stage: T0, T2, T3, T4, T7, T8 RIFLE category: T0, T2, T3, T4, T7, T8 Urin output: T0, T1, T3-T4 Coagulation: T0, T2, T3 C-RP: T0, T2, T3 (S)AEs/(S)ARs T0-T8 Blood loss - RBC:T4 & intra-op: T2 LOS-H, LOS-ICU, Fit for discharge - H & ICU: daily MV: T0-T5 Mortality (+ cause): T2-T9 RRT: T2 - T5 new RRT after POD 7 or H- discharge: T7, T8, T9 IP intake, fluid in-/output, fluid bal: T0-T4 T: T0, T2-T4 HR, MAP, SAP, DAP, CVP: T0, T1 (at least q 30 min), T2-T4 vol guide: during IP admin ABGA: T0 + T2 (all); T3 + T4 (only Hb, Hct, lactate) ScvO2: T0, T2, T3 S Elyte: T0, T2, T3 Maj compl: T3-T8 |
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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 | Yes |
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) | 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 | 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) | 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 | 36 |
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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T8, i.e. day 90 ± 14 days of the last patient |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |