Clinical trial NCT03980132: Preoperative Preparation With Lugol Solution in Patients With Graves-Basedow Disease.
Official title: Randomized Clinical Trial, Blinded for the Researcher and Multicenter, to Evaluate the Efficacy and Safety of Preoperative Preparation With Lugol Solution in Euthyroid Patients With Graves-Basedow Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hyperthyroidism, Autoimmune
Keywords: Thyroid Surgery
Grave' Disease
Lugol Solution
Lead sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
Sponsor class: OTHER
First posted: 2019-06-10
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Currently, both the American Thyroid Association and the European Thyroid Association recommend the use of Lugol Solution (LS) in the preparation of patients undergoing thyroidectomy for Graves' disease (GD), but their recommendations are based on a low level of evidence. This means that its use is not generalized among the different endocrine surgery units.

Methods:

Study population: 270 patients (135 patients in each arms) undergoing total thyroidectomy (TT) due to GD in Spanish hospitals, which perform a minimum of 100 thyroidectomies a year, at least 10 of them for GD.

Variables:

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 radioiodine, 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, international normalized ratio(INR), creatinine, potassium, total calcium, albumin, total proteins, parathormone (PTH), 25-hydroxide-vitamin D, free T4 and / or free T3, TSH, thyroid stimulating immunoglobulin (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 recurrent laryngeal nerve.
* 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, paralysis of the recurrent laryngeal nerve, postoperative hematoma, surgical site infection or death.
* Debit for surgical drains.
* Postoperative hospital long of stay.
* Anatomopathological variables: histological diagnosis compatible with GD and existence of parathyroid glands in the surgical specimen.
* Long-term complications: hypocalcemia and/or permanent vocal cord paralysis longer than 6 months


Eligibility criteria: Inclusion Criteria:

Patients who meet all of the following criteria will be eligible:

* 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 GD.
* 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.

Exclusion Criteria:

The participant can not participate in the study if he / she presents any of the following circumstances:

* 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 LS.
* 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.

Primary outcomes:
measure: Postoperative complications
timeFrame: 30 days after surgery
Secondary outcomes:
measure: Surgical difficulty
timeFrame: Intraoperatively
measure: Intraoperative hemorrhage
timeFrame: Intraoperatively
measure: Surgical time.
timeFrame: Intraoperatively.
measure: Intraoperative neuromonitoring.
timeFrame: Intraoperatively.
measure: Postoperative Long of Stay
timeFrame: 30 days after surgery
measure: Readmissions
timeFrame: 30 days after surgery.
measure: Permanent complications
timeFrame: 180 days after surgery
measure: Adverse events
timeFrame: 180 days after surgery
Other outcomes:
Locations:
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: San Sebastián
country: Spain
facility: Hospital Universitario Donostia
state: Guipúzcoa
city: Santiago De Compostela
country: Spain
facility: Hospital Clínico Universitario
state: La Coruña
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario Insular de Gran Canaria
state: Las Palmas
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Madrid
city: El Palmar
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
state: Murcia
city: Baracaldo
country: Spain
facility: Hospital Universitario de Cruces
state: Vizcaya
city: Bilbao
country: Spain
facility: Hospital Universitario de Basurto
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Universitario del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital Universitario de La princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clínico Universitario
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
Study officials:
References:
citation: Munoz de Nova JL, Franch-Arcas G, Mejia-Abril GP, Flores-Ruiz ME, Munoz-Perez N, Pintos-Sanchez E, Guadarrama Gonzalez FJ, Valdes de Anca A, Mercader-Cidoncha E, de la Quintana-Basarrate A, Osorio-Silla I, Ros-Lopez S, Gallego-Otaegui L, Santos-Molina E, Martinez-Nieto C, Gamborino-Carames E, Artes-Caselles M, Lorente-Poch L, Garcia-Carrillo M, Moreno-Llorente P, Marin-Velarde C, Ortega-Serrano J, Martos-Martinez JM, Vidal-Perez O, Luengo-Pierrard P, Villar-Del-Moral JM. Efficacy and safety of preoperative preparation with Lugol's iodine solution in euthyroid patients with Graves' disease (LIGRADIS Trial): Study protocol for a multicenter randomized trial. Contemp Clin Trials Commun. 2021 Jun 15;22:100806. doi: 10.1016/j.conctc.2021.100806. eCollection 2021 Jun.