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 |
Tratamiento de hipovolemia cirugía abdominal electiva |
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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 |
Disminución del volumen sanguíneo (hipovolemia) debida a sangrado intenso durante la cirugía abdominal programada |
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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 | 19.1 |
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 |
Investigar la seguridad de una solución 6% HES (Volulyte 6%) frente a una solución electrolítica (Ionolyte) en pacientes sometidos a cirugía abdominal electiva. |
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E.2.2 | Secondary objectives of the trial |
Further investigation of safety and efficacy of the applied products |
Investigación adicional sobre la seguridad y la eficacia de los productos de investigación empleados |
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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 |
Pacientes adultos de ambos géneros > 40 y ≤ 85 años de edad. Las mujeres en edad fértil deben dar un resultado negativo en un test de embarazo estándar (orina o suero) Pacientes sometidos a cirugía abdominal electiva con una pérdida esperada de sangre ≥ 500 ml Estado ASA II-III Consentimiento informado firmado |
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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 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) |
Hipersensibilidad a la sustancias activas o a cualquier excipiente de los productos médicos en investigación Peso corporal ≥ 140 kg Sepsis Quemaduras Trastorno renal (estado AKIN ≥ 1) o terapia de reemplazo renal aguda o crónica Hemorragia intracraneal o cerebral Pacientes críticos (típicamente admitidos en la unidad de cuidados intensivos) Hiperhidratación Deshidratación Edema pulmonary Insuficiencia cardiaca congestiva Hipernatremia severa Hipercloremia severa Hiperpotasemia Alcalosis metabólica Función hepática gravemente deteriorada Coagulopatía severa Pacientes con trasplante de órganos Participación simultánea en otros ensayos clínicos de intervención (estudios con medicamentos o dispositivos médicos) |
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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. |
Diferencias en la media de la tasa de filtración glomerular estimada (TFG estimada: TFGe) (calculado desde los niveles más altos de cistatina-C medidos durante los días 1-3 postoperatorios (DOP 1-3)) entre los dos grupos de tratamiento. |
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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. |
Los niveles de cistatina C se determinarán en los días posoperatorios 1-3. La Tasa de Filtración Glomerular estimada (TFGe) se calculará a partir del nivel más alto de cistatina C durante este período. |
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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) 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 to 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) ± 14 days T9 (1 year PO) ± 30 days |
Seguridad -Función renal: Cistatina-C, Creatinina sérica (Crs), Tasa de filtración glomerular estimada (TFGe) basada en cistatina-C, Media de TFG estimada basada en cistatina-C, Crs basado en TFGe, Escalas AKIN y RIFLE, Producción de orina -Coagulación: Recuento plaquetario, Relación normalizada internacional (INR), Tiempo activación parcial de la tromboplastina (PTTa) - Inflamación: Proteína C-reactiva - Eventos adversos: Eventos o reacciones adversos (serios) ((S)EAS/(S)RAS) - Pérdida calculada de células rojas sanguíneas (CRS) - Pérdida de sangre estimada intra-operatoria
Resultados: Duración de la estancia hospitalaria (LOS), Duración de la estancia hospitalaria en la unidad de cuidados intensivos (UCI) (si aplica), Razón del alta UCI/hospital, Horas de ventilación mecánica, Mortalidad dentro o fuera del hospital (incluida causa), Terapia de reemplazo renal (TRR)
Eficacia -Administración de fluidos -Administración de volumen de producto en investigación - Balance de fluidos: Entrada y salida de fluidos - Signos vitales/hemodinámicos: Ritmo cardiaco (FC), Temperatura (T), Presión arterial media (PAM), Presión arterial sistólica (PAS), Presión arterial diastólica (PAD), Presión venosa central (PVC) (si está disponible) - Al menos uno de los siguiente parámetros para evaluar la respuesta a volumen y orientar la administración del producto en investigación dentro del algoritmo de volume: Volumen sistólico (VS), Variación del volumen sistólico (VVS), Índice de volumen sistólico (IVS), Variación en la presión de pulso (VPP), Presión arterial media (PAM)
Datos de laboratorio -Análisis de gases arteriales (GAB): Presión parcial de dióxido de carbono (pCO2), Presión parcial de oxígeno (pO2), Bicarbonato (HCO3-), Saturación arterial de oxígeno (SaO2), Hemoglobina (Hb), Hematocrito (Hct), pH, Exceso de bases, Lactato -Saturación venosa central de oxígeno (si está disponible) -Electrolitos en suero: Sodio (Na+), Potasio (K+), Calcio (Ca2+), Cloro (Cl-) - Complicaciones postoperatorias mayores (incluyendo renales)
Calendario de visitas Selección (una semana antes de la cirugía) T0 Base de referencia (Depués de la aleatorización y antes de la inducción de la anestesia) T1 (Durante la cirugía) T2 (Final de la cirugía) T3 (1ª mañana post-operatorio) T4 (2º hasta 3º mañana postoperatoria) T5 (4º hasta 7º mañana postoperatoria, o alta hospitalaria, lo que ocurra primero) T6 (8º hasta 10º mañana postoperatoria, o alta hospitalaria, lo que ocurra primero) T7 (día 28 tras la cirugía, ± 5 días) T8 (día 90 tras la cirugía, ± 14 días) T9 (1 año tras la cirugía, ± 30 días) |
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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, T2-T4 Coagulation: T0, T2, T3 C-RP: T0, T2, T3 (S)AEs/(S)ARs: T0-T5 Blood loss - RBC:T4 & intra-op: T2 LOS-H, LOS-ICU, Fit for discharge - H & ICU: daily MV: T0-T5 Mortality (+ cause): T2-T5, T7, T8 RRT: T2-T5 new RRT after POD 7 or H- discharge: T7, T8 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-T5, T7, T8 |
Cistatina-C: T0, T2-T8 Crs: T0, T2, T3, T4, T7, T8 TFGe basada en cistatina-C: T0, T2, T3, T4, T7, T8 Media de TFG estimada basada en cistatina-C: T3-T6 Crs basado en TFGe: T0, T2, T3, T4, T7, T8 Escalas AKIN y RIFLE: T0, T2, T3, T4, T7, T8 Producción de orina: T0, T2-T4 Coagulación: T0, T2, T3 C-RP: T0, T2, T3 (S)EAs/(S)RAs: T0-T5 Pérdida sangre- CRS: T4 & Durante la cirugía: T2 LOS-H, LOS-UCI, Razón del alta UCI/hospital:diario VM: T0-T5 Mortalidad: T2-T5, T7, T8 TRR: T2-T5 TRR: T7, T8 Balance de fluidos: T0-T4 T: T0, T2-T4 FC, PAM, PAS, PAD, PVC: T0, T1,T2-T4 Administración de volumen de producto en investigación: T1-T3 GAB: T0 + T2 (todas); T3 + T4 (solo Hb, Hct, lactato) ScvO2: T0, T2, T3 Electrolitos: T0, T2, T3 Compl myores: T3-T5, T7, 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) | 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 | 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 | 8 |
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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POD7 or hospital discharge, whatever occurs first for 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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |