E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Graves-Basedow disease |
Enfermedad de Graves-Basedow |
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E.1.1.1 | Medical condition in easily understood language |
Graves-Basedow disease |
Enfermedad de Graves-Basedow |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065624 |
E.1.2 | Term | Graves-Basedow disease |
E.1.2 | System Organ Class | 100000004860 |
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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 |
To analyze whether, in euthyroid patients undergoing TT due to GD, preoperative non-preparation with LS increases the appearance of postoperative complications compared to the use of LS preparation. |
Analizar si, en pacientes eutiroideos sometidos a tiroidectomía total por enfermedad de Graves, la no preparación preoperatoria con solución de Lugol incrementa la aparición de complicaciones postoperatorias frente a la utilización de dicha preparación. |
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E.2.2 | Secondary objectives of the trial |
- To analyze whether, in patients undergoing TT, preoperative non-preparation with LS influences intraoperative results. - To analyze whether, in patients undergoing TT, preoperative non-preparation with LS influences the postoperative long of stay or the rate of readmissions, when compared with the group of patients who do receive such preparation. - To analyze if, in patients undergoing TT, preoperative non-preparation with LS does not increase the appearance of permanent complications, including hypoparathyroidism or RLN injury, when compared with the group of patients who do they receive this preparation. - Determine the safety profile of the use of the LS. - Detect if there are subgroups of patients undergoing TT, in which the non-preparation with LS is particularly beneficial or harmful. - Compare the results obtained according to the technical variations used by each unit. |
- Analizar si, en pacientes sometidos a TT, la no preparación preoperatoria con SL influye en los resultados intraoperatorios. - Analizar si, en pacientes sometidos a TT, la no preparación preoperatoria con SL influye en la estancia postoperatoria o la tasa de reingresos urgentes, cuando se comparan con el grupo de pacientes que sí reciben dicha preparación. - Analizar si, en pacientes sometidos a TT, la no preparación preoperatoria con SL no incrementa la aparición de complicaciones permanentes, incluyendo hipoparatiroidismo o lesión del nervio recurrente, cuando se comparan con el grupo de pacientes que sí reciben dicha preparación. - Determinar el perfil de seguridad del uso de la SL. - Detectar si existen subgrupos de pacientes sometidos a TT, en los que la no preparación con SL sea particularmente beneficiosa o perjudicial. - Comparar los resultados obtenidos en función de las variaciones técnicas empleadas por cada unidad. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- The age of the patient must be over 18 years of age. - The patient or his / her tutor, in cases where this is the case, has the capacity to understand the study and agrees to participate in it, by signing the corresponding informed consent document. - Patients who have been diagnosed with GD, defined as the existence of hyperthyroidism (TSH < lower limit of laboratory normality associated with TSI > upper limit of laboratory normality) that present ultrasonographic data (diffuse vascularization increase) and / or scintigraphy (diffuse uptake of the radioisotope) compatible with EG. - Euthyroid patients (free T4 and / or free T3 within the normal range of the laboratory) at the time of randomization, and under treatment with AT drugs (propylthiouracil, carbimazole or methimazole). - The patient must be proposed for total thyroidectomy, using a transcervical approach. |
- La edad del enfermo debe ser mayor de 18 años. - El paciente o su tutor, en los casos que así sea, tiene la capacidad para entender el estudio y acepta participar en el mismo, firmando el correspondiente documento de consentimiento informado. - Pacientes que hayan sido diagnosticados de EG, definida como la existencia de hipertiroidismo (TSH < límite inferior de la normalidad del laboratorio [LIN]) asociado a una elevación en los TSI (TSI > límite superior de la normalidad del laboratorio [LSN]) que presenten datos ecográficos (aumento difuso de la vascularización) y/o gammagráficos (captación difusa del radioisótopo) compatibles con EG. - Pacientes eutiroideos (T4 libre y/o T3 libre dentro del rango de normalidad del laboratorio) en el momento de la aleatorización, y bajo tratamiento con fármacos AT (propiltiouracilo, carbimazol o metimazol). - El paciente debe estar propuesto para tiroidectomía total, mediante abordaje transcervical. |
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E.4 | Principal exclusion criteria |
- Prior cervicotomy by surgical intervention on the thyroid or parathyroid gland. - Associated hyperparathyroidism that requires associating a parathyroidectomy in the same surgical act. - Associated thyroid cancer that requires adding a lymph node dissection of the central or lateral compartment in the same surgical time. - Iodine allergy. - Consumption of lithium or amiodarone between randomization and administration of SL. - Patients with category IV of the anesthetic risk classification of the American Society of Anesthesiologists (ASA). - Women who breastfeed during the administration of the LS or in the month after it. - Preoperative palsy of a vocal cord verified by laryngoscopy. - Surgery performed by training specialists, or by staff not specifically dedicated to endocrine surgery. - Surgery not performed under general anesthesia. - Endoscopic surgery, video assisted or by remote approach. - Surgery performed in out-patient settings. - Current drug consumption or alcohol abuse that could interfere with meeting the study requirements. - Participation in any other trial with medications in the month prior to randomization. |
- Cervicotomía previa por intervención quirúrgica sobre la glándula tiroides o paratiroides. - Hiperparatiroidismo asociado que requiera asociar una paratiroidectomía en el mismo acto quirúrgico. - Cáncer de tiroides asociado que requiera añadir una disección ganglionar del compartimento central o lateral en el mismo acto quirúrgico. - Alergia al yodo. - Consumo entre la aleatorización y la administración de la SL de litio o amiodarona. - Pacientes con categoría IV de la clasificación de riesgo anestésico de la American Society of Anesthesiologists (ASA) (19). - Mujeres que den lactancia materna durante la administración de la SL o en el mes posterior a la misma. - Parálisis preoperatoria de una cuerda vocal constatada mediante laringoscopia. - Cirugía realizada por especialistas en formación, o por staff no dedicado específicamente a la cirugía endocrina. - Cirugía no realizada bajo anestesia general. - Cirugía endoscópica, videoasistida o mediante abordaje remoto. - Cirugía realizada en régimen de cirugía mayor ambulatoria. - Consumo actual de drogas o abuso de alcohol que pudiera interferir con el cumplimiento de los requisitos de estudio. - Participación en cualquier otro ensayo con medicamentos en el mes previo a la aleatorización. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The main variable will therefore be the appearance of at least one postoperative complication: hypoparathyroidism, RLN injury, postoperative hematoma, SSI or postoperative death. |
La variable principal será por tanto la aparición de al menos una complicación postoperatoria: hipoparatiroidismo, lesión del nervio recurrente, hematoma postoperatorio, infección de la herida quirúrgica o muerte postoperatoria. |
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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) |
Preoperative variables - Demographic variables: birthdate, gender and ethnicity. - Drugs allergies. Allergy to iodine. - Personal history and usual treatment. - Aspects related to the GD: date of diagnosis, use of AT drugs and/or RI, existence of ophthalmopathy, existence of cervical compression symptoms and indication of surgery. - Physical exploration: body mass index, pulse at rest and blood pressure and cervical palpation. - Laboratory tests: hematocrit, leukocytes, neutrophils, platelets, INR, creatinine, potassium, total calcium, albumin, total proteins, PTH, 25-OH-vitamin D, free T4 and / or free T3, TSH, TSI. - Classification of the anesthetic risk of ASA. - Cervical ultrasound: existence of thyroid nodules and volume of the thyroid. - Mobility of the vocal cords evaluated by laryngoscopy. - Compliance with assigned treatment: the patient assigned to the LS arm must have consumed at least 80% of the total dose indicated.
Intraoperative variables - Surgical time. - Antibiotic prophylaxis. - Intraoperative hemorrhage. - Thyroidectomy Difficulty Scale. - Loss of electromyographic signal during neural intraoperative monitorization. - Accidental parathyroidectomy. - Section or obvious lesion of the NLR. - Trachea or esophagus perforation. - Weight of the gland. - Electrosurgical hemostasis system used during the intervention. - Maneuvers used to check hemostasis. - Hemostats used during the intervention. - Use of drainage. - Definitive surgical technique: TT, unilateral or bilateral subtotal thyroidectomy or hemithyroidectomy.
Postoperative variables - Early complications: hypoparathyroidism, RLN paralysis of the NLR, postoperative hematoma, SSI or death. - Debit for surgical drains. - Postoperative hospital long of stay. - Anatomopathological variables: histological diagnosis compatible with EG and existence of parathyroid glands in the surgical specimen. - Long-term complications: hypocalcemia and/or permanent vocal cord paralysis longer than 6 months |
Variables preoperatorias - Variables demográficas: fecha de nacimiento, género y etnia - Alergias medicamentosas. Alergia a yodo - Antecedentes personales y tratamiento habitual - Aspectos relacionados con la EG: fecha de diagnóstico, uso de fármacos AT, uso previo de RI, existencia de oftalmopatía, existencia de clínica compresiva cervical, indicación de la cirugía - Exploración física: índice de masa corporal, pulso en reposo y presión arterial, y palpación cervical - Pruebas de laboratorio: hematocrito, leucocitos, neutrófilos, plaquetas, INR, creatinina, potasio, calcio total, albúmina, proteínas totales, PTH, 25-OH-vitamina D, T4 libre y/o T3 libre, TSH, TSI - Clasificación del riesgo anestésico de la ASA - Ecografía cervical: se recogerá la existencia de nódulos tiroideos y volumen del tiroides - Movilidad de las cuerdas vocales evaluada mediante laringoscopia - Cumplimiento del tratamiento asignado: el paciente asignado al brazo de la SL deberá haber consumido al menos el 80% de la dosis total indicada
Variables intraoperatorias - Tiempo quirúrgico - Profilaxis antibiótica - Hemorragia intraoperatoria - Thyroidectomy Difficulty Scale - Pérdida de señal electromiográfica detectada mediante NMI - Paratiroidectomía accidental - Sección o lesión evidente del NLR - Perforación de tráquea o esófago - Peso de la glándula - Sistema de hemostasia electroquirúrgica empleado durante la intervención - Maniobras empleadas para la comprobación de la hemostasia - Hemostáticos empleados durante la intervención - Uso de drenaje en el lecho quirúrgico - Técnica quirúrgica definitiva: TT, tiroidectomía subtotal uni o bilateral o hemitiroidectomía
Variables postoperatorias - Complicaciones precoces: hipoparatiroidismo, parálisis del NLR, hematoma postoperatorio, infección del sitio quirúrgico o éxitus - Débito por los drenajes quirúrgicos - Estancia hospitalaria postoperatoria - Variables anatomopatológicas: diagnóstico histológico compatible con EG y existencia de glándulas paratiroides en la pieza quirúrgica. - Complicaciones a largo plazo: hipocalcemia y/o parálisis del NLR permanente |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
No tratamiento |
Non treatment |
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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 | 3 |
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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LVLS |
Última visita del último paciente |
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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 | 21 |
E.8.9.1 | In the Member State concerned days | |