Hyperthyroidism, AutoimmunePhase 4LIGRADISNCT03980132
Preoperative Preparation With Lugol Solution in Patients With Graves-Basedow Disease.
A Phase 4 study testing Lugols Strong Iodine in people with Hyperthyroidism, Autoimmune, run by Jesús María Villar del Moral at 21 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperthyroidism, Autoimmune
- What is being tested?
- Lugols Strong Iodine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 184 participants
- Where
- 21 sitesSpain
- Study dates
- 25 Nov 2019to 30 Nov 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
Spain21 sites
Hospital Universitario de Cruces
Barakaldo, Vizcaya, 48903
Hospital Universitario del Mar
Barcelona, 08003
Hospital Clinic
Barcelona, 08036
Hospital Universitario de Basurto
Bilbao, Vizcaya, 48013
Hospital Clínico Universitario Virgen de la Arrixaca
El Palmar, Murcia, 30120
Hospital Universitario Virgen de las Nieves
Granada, 18014
Hospital Universitario de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital Universitario Insular de Gran Canaria
Las Palmas de Gran Canaria, Las Palmas, 35016
Hospital Universitario de La princesa
Madrid, 28006
Hospital General Universitario Gregorio Marañón
Madrid, 28007
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid, 28222
Complejo Asistencial Universitario de Salamanca
Salamanca, 37007
Hospital Universitario Donostia
San Sebastián, Guipúzcoa, 20014
Hospital Clínico Universitario
Santiago de Compostela, La Coruña, 15706
Hospital Universitario Virgen Macarena
Seville, 41009
Hospital Universitario Virgen del Rocío
Seville, 41013
Hospital Clínico Universitario
Valencia, 16010
Hospital Clínico Universitario Lozano Blesa
Zaragoza, 50009
About this study
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.
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:
Read more
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
- Conditions
- Hyperthyroidism, Autoimmune
- Being tested
- Lugols Strong Iodine
- Keywords
- Thyroid Surgery, Grave' Disease, Lugol Solution
- Medical subject headings
- Graves Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lugols Strong IodineDrug
5 L.I. drops / 8 hours for 10 days before surgery
| Study group | Role | What they receive |
|---|---|---|
| Preoperative Lugol Solution preparation | Experimental | Patients will receive Lugol Solution preparation for 10 days before thyroidectomy Receives: Drug: Lugols Strong Iodine |
| No preparation | No intervention | Patients will not receive preparation before thyroidectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days after surgery
Secondary outcomes (8)
Surgical difficulty
Score of the difficulty of the surgery by the surgeon through the Thyroidectomy Difficulty Scale.
Measured: Intraoperatively
Intraoperative hemorrhage
Amount of blood lost during the thyroidectomy in dL.
Measured: Intraoperatively
Surgical time.
Time from surgical incision to skin closure in minutes.
Measured: Intraoperatively.
Intraoperative neuromonitoring.
Rate of patients with loss of electromyographic signal during intraoperative neuromonitoring.
Measured: Intraoperatively.
Postoperative Long of Stay
Days to hospital discharge after surgery.
Measured: 30 days after surgery
Readmissions
Rate of readmissions.
Measured: 30 days after surgery.
Permanent complications
Rate of patients with permanent complications, including hypoparathyroidism or recurrent laryngeal nerve injury.
Measured: 180 days after surgery
Adverse events
Number of patients with an adverse event after administration of Lugol solution.
Measured: 180 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2019
- Study start25 Nov 2019
- Primary completion30 Nov 2023
- Study completion30 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hyperthyroidism, AutoimmuneStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 184 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jesús María Villar del Moral
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jesús María Villar del Moral, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03980132
- Sponsor's protocol ID
- LIGRADIS
- Acronym
- LIGRADIS
- Status last verified
- Mar 2024
- First submitted
- 30 May 2019
- Last updated
- 6 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34195471
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03980132
- Acronym / sponsor ID
- LIGRADIS / LIGRADIS
- Conditions
- Hyperthyroidism, Autoimmune
- Keywords
- Thyroid Surgery, Grave' Disease, Lugol Solution
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 184 participants (actual)
- Lead sponsor
- Jesús María Villar del MoralUniversity, hospital or other
- Study start
- 25 Nov 2019 (actual)
- Primary completion
- 30 Nov 2023 (actual)
- Study completion
- 30 Nov 2023 (actual)
- First posted
- 10 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Preoperative Lugol Solution preparation | Experimental | Drug: Lugols Strong IodinePatients will receive Lugol Solution preparation for 10 days before thyroidectomy |
| No preparation | No intervention | –Patients will not receive preparation before thyroidectomy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lugols Strong Iodine5 L.I. drops / 8 hours for 10 days before surgery | Drug | Preoperative Lugol Solution preparation |
Primary outcome
Postoperative complications
Time frame: 30 days after surgery
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.
8 secondary outcomes
Surgical difficulty
Time frame: Intraoperatively
Intraoperative hemorrhage
Time frame: Intraoperatively
Surgical time.
Time frame: Intraoperatively.
Intraoperative neuromonitoring.
Time frame: Intraoperatively.
Postoperative Long of Stay
Time frame: 30 days after surgery
Readmissions
Time frame: 30 days after surgery.
Permanent complications
Time frame: 180 days after surgery
Adverse events
Time frame: 180 days after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2024.
- Results publication: PubMed 34195471Munoz 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lugols Strong Iodine in people with Hyperthyroidism, Autoimmune, run by Jesús María Villar del Moral at 21 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postoperative complications (time frame: 30 days after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03980132, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2024.