search
Back to results

Preoperative Preparation With Lugol Solution in Patients With Graves-Basedow Disease. (LIGRADIS)

Primary Purpose

Hyperthyroidism, Autoimmune

Status
Unknown status
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Lugols Strong Iodine
Sponsored by
Jesús María Villar del Moral
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyperthyroidism, Autoimmune focused on measuring Thyroid Surgery, Grave' Disease, Lugol Solution

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital Universitario de BellvitgeRecruiting
  • Hospital Universitario DonostiaRecruiting
  • Hospital Clínico UniversitarioRecruiting
  • Hospital Universitario Insular de Gran Canaria
  • Hospital Universitario Puerta de HierroRecruiting
  • Hospital Clínico Universitario Virgen de la Arrixaca
  • Hospital Universitario de CrucesRecruiting
  • Hospital Universitario de BasurtoRecruiting
  • Hospital Universitario del MarRecruiting
  • Hospital ClinicRecruiting
  • Hospital Universitario Virgen de las NievesRecruiting
  • Hospital Universitario de La princesaRecruiting
  • Hospital General Universitario Gregorio MarañónRecruiting
  • Hospital Universitario Ramón y CajalRecruiting
  • Hospital Universitario Fundación Jiménez DíazRecruiting
  • Hospital Universitario 12 de OctubreRecruiting
  • Complejo Asistencial Universitario de SalamancaRecruiting
  • Hospital Universitario Virgen MacarenaRecruiting
  • Hospital Universitario Virgen del RocíoRecruiting
  • Hospital Clínico UniversitarioRecruiting
  • Hospital Clínico Universitario Lozano BlesaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Preoperative Lugol Solution preparation

No preparation

Arm Description

Patients will receive Lugol Solution preparation for 10 days before thyroidectomy

Patients will not receive preparation before thyroidectomy

Outcomes

Primary Outcome Measures

Postoperative complications
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. The main variable will be the rate of postoperative complication: hypoparathyroidism, recurrent laryngeal nerve injury, hematoma, surgical site infection or death.

Secondary Outcome Measures

Surgical difficulty
Score of the difficulty of the surgery by the surgeon through the Thyroidectomy Difficulty Scale.
Intraoperative hemorrhage
Amount of blood lost during the thyroidectomy in dL.
Surgical time.
Time from surgical incision to skin closure in minutes.
Intraoperative neuromonitoring.
Rate of patients with loss of electromyographic signal during intraoperative neuromonitoring.
Postoperative Long of Stay
Days to hospital discharge after surgery.
Readmissions
Rate of readmissions.
Permanent complications
Rate of patients with permanent complications, including hypoparathyroidism or recurrent laryngeal nerve injury.
Adverse events
Number of patients with an adverse event after administration of Lugol solution.

Full Information

First Posted
May 30, 2019
Last Updated
July 4, 2021
Sponsor
Jesús María Villar del Moral
search

1. Study Identification

Unique Protocol Identification Number
NCT03980132
Brief Title
Preoperative Preparation With Lugol Solution in Patients With Graves-Basedow Disease.
Acronym
LIGRADIS
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

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Unknown status
Study Start Date
November 25, 2019 (Actual)
Primary Completion Date
January 31, 2023 (Anticipated)
Study Completion Date
September 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jesús María Villar del Moral

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperthyroidism, Autoimmune
Keywords
Thyroid Surgery, Grave' Disease, Lugol Solution

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Care ProviderInvestigator
Allocation
Randomized
Enrollment
270 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Preoperative Lugol Solution preparation
Arm Type
Experimental
Arm Description
Patients will receive Lugol Solution preparation for 10 days before thyroidectomy
Arm Title
No preparation
Arm Type
No Intervention
Arm Description
Patients will not receive preparation before thyroidectomy
Intervention Type
Drug
Intervention Name(s)
Lugols Strong Iodine
Intervention Description
5 L.I. drops / 8 hours for 10 days before surgery
Primary Outcome Measure Information:
Title
Postoperative complications
Description
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. The main variable will be the rate of postoperative complication: hypoparathyroidism, recurrent laryngeal nerve injury, hematoma, surgical site infection or death.
Time Frame
30 days after surgery
Secondary Outcome Measure Information:
Title
Surgical difficulty
Description
Score of the difficulty of the surgery by the surgeon through the Thyroidectomy Difficulty Scale.
Time Frame
Intraoperatively
Title
Intraoperative hemorrhage
Description
Amount of blood lost during the thyroidectomy in dL.
Time Frame
Intraoperatively
Title
Surgical time.
Description
Time from surgical incision to skin closure in minutes.
Time Frame
Intraoperatively.
Title
Intraoperative neuromonitoring.
Description
Rate of patients with loss of electromyographic signal during intraoperative neuromonitoring.
Time Frame
Intraoperatively.
Title
Postoperative Long of Stay
Description
Days to hospital discharge after surgery.
Time Frame
30 days after surgery
Title
Readmissions
Description
Rate of readmissions.
Time Frame
30 days after surgery.
Title
Permanent complications
Description
Rate of patients with permanent complications, including hypoparathyroidism or recurrent laryngeal nerve injury.
Time Frame
180 days after surgery
Title
Adverse events
Description
Number of patients with an adverse event after administration of Lugol solution.
Time Frame
180 days after surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jesús María Villar del Moral
Phone
+34958020349
Email
jesusm.villar.sspa@juntadeandalucia.es
First Name & Middle Initial & Last Name or Official Title & Degree
José Luis Muñoz de Nova
Phone
+34915202448
Email
jmunoz@salud.madrid.org
Facility Information:
Facility Name
Hospital Universitario de Bellvitge
City
Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pablo Moreno Llorente
Phone
+34932607621
Email
pmoreno@bellvitgehospital.cat
Facility Name
Hospital Universitario Donostia
City
San Sebastián
State/Province
Guipúzcoa
ZIP/Postal Code
20014
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lander Gallego Otaegui
Phone
+34943007000
Email
lander.gallegootaegui@osakidetza.net
Facility Name
Hospital Clínico Universitario
City
Santiago De Compostela
State/Province
La Coruña
ZIP/Postal Code
15706
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elena Gamborino Caramés
Phone
+34981951432
Email
elena.gamborino.carames@sergas.es
Facility Name
Hospital Universitario Insular de Gran Canaria
City
Las Palmas De Gran Canaria
State/Province
Las Palmas
ZIP/Postal Code
35016
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
María Isabel Gutiérrez Giner
Phone
+34928441652
Email
mgutgin@gobiernodecanarias.org
Facility Name
Hospital Universitario Puerta de Hierro
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariano Artés Caselles
Phone
+34911916184
Email
mariano.artes@salud.madrid.org
Facility Name
Hospital Clínico Universitario Virgen de la Arrixaca
City
El Palmar
State/Province
Murcia
ZIP/Postal Code
30120
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
José Manuel Rodríguez González
Phone
+34968369500
Email
jmrodri@um.es
Facility Name
Hospital Universitario de Cruces
City
Baracaldo
State/Province
Vizcaya
ZIP/Postal Code
48903
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aitor de la Quintana Basarrate
Phone
+34946006068
Email
aitor.quintanadelabasarrate@osakidetza.eus
Facility Name
Hospital Universitario de Basurto
City
Bilbao
State/Province
Vizcaya
ZIP/Postal Code
48013
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maitane García Carrillo
Phone
+34944006000
Email
maitane.garciacarrillo@osakidetza.eus
Facility Name
Hospital Universitario del Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leyre Lorente Poch
Phone
+34932483000
Email
lorentepoch@live.com
Facility Name
Hospital Clinic
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Óscar Vidal Pérez
Phone
+34932275718
Email
ovidal@clinic.cat
Facility Name
Hospital Universitario Virgen de las Nieves
City
Granada
ZIP/Postal Code
18014
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jesús María Villar del Moral
Phone
+34958020349
Email
jesusm.villar.sspa@juntadeandalucia.es
First Name & Middle Initial & Last Name & Degree
Nuria Muñoz Pérez
Phone
+34958020349
Email
numupe@gmail.com
Facility Name
Hospital Universitario de La princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
José Luis Muñoz de Nova, MD
Phone
+34915202447
Email
jmunoz@salud.madrid.org
First Name & Middle Initial & Last Name & Degree
José Luis Muñoz de Nova, MD
Facility Name
Hospital General Universitario Gregorio Marañón
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Enrique Mercader Cidoncha
Phone
+34915868348
Email
enrique.mercader@salud.madrid.org
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joaquín Gómez Ramírez
Phone
+34913368000
Email
joaquin.gomez@salud.madrid.org
Facility Name
Hospital Universitario Fundación Jiménez Díaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Irene Osorio Silla
Phone
+34915504800
Email
irene.osorio@quironsalud.es
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francisco Javier Guadarrama González
Phone
+34913908000
Email
fjavier.guadarrama@salud.madrid.org
Facility Name
Complejo Asistencial Universitario de Salamanca
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guzmán Franch Arcas
Phone
+34923291100
Email
gfranch@saludcastillayleon.es
Facility Name
Hospital Universitario Virgen Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Consuelo Marín Velarde
Phone
+34955008000
Email
consuelomarinvelarde@hotmail.com
Facility Name
Hospital Universitario Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Manuel Martos Martínez
Phone
+34955012313
Email
juan.martos.sspa@juntadeandalucia.es
Facility Name
Hospital Clínico Universitario
City
Valencia
ZIP/Postal Code
16010
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joaquín Ortega Serrano
Phone
+34961973833
Email
joaquin.ortega@uv.es
Facility Name
Hospital Clínico Universitario Lozano Blesa
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susana Ros López
Phone
+34976768884
Email
susanaros44@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34195471
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.
Results Reference
result

Learn more about this trial

Preoperative Preparation With Lugol Solution in Patients With Graves-Basedow Disease.

We'll reach out to this number within 24 hrs