Clinical trial NCT04856488: Preoperative Lugol's Solution in Graves' Disease and Toxic Nodular Goiter
Official title: Preoperative Lugol's Solution in Graves' Disease and Toxic Nodular Goiter
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hyperthyroidism
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2021-04-23
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess if preoperative treatment with Lugol's solution prior to thyroidectomy can reduce the surgical complications hypoparathyroidism and laryngeal nerve palsy

Detailed description: Current practice in Sweden before thyroidectomy due to hyperthyroidism is preoperative treatment with antithyroid drugs (ATD) to all patients with Graves' disease and in cases of toxic nodular goiter with pronounced hyperthyroidism. Iodine solution is administered preoperatively in selected cases of Graves' disease where ATD is intolerable. In the cases where iodine is used it is in the form of extemporaneous prepared iodine potassium iodide solution (Lugol 5%). The dose varies in clinical studies. In American and Swedish guidelines the dose is 5-10 drops 3 times per day for 10 days prior to surgery. American guidelines recommend iodine as preoperative treatment i Graves' disease but this is based on sparse evidence. Iodine as preoperative treatment in toxic nodular goiter has yet not been studied.

The purpose of this study is to assess if preoperative treatment with Lugol's solution prior to thyroidectomy due to hyperthyroidism reduce the surgical complications hypoparathyroidism and laryngeal nerve palsy.

Before including toxic nodular goiters accepted for surgery, a pilot study will be performed on 20 patients with toxic nodular goiter. They will receive Lugol solution 3 times per day for ten days and thyroid hormone levels will be measured day 0, day 3-4, day 6-7 and after 10 days of Lugol treatment. Heart rate assessed and ThyPRO39 filled out before and after treatment.

Eligibility criteria: Inclusion Criteria:

* Hyperthyroidism accepted for thyroidectomy due to toxic nodular goiter with free T4 \<30 pmol/L or Graves' disease
* Signed informed consent

Exclusion Criteria:

* Unstable coronary artery disease
* Previous thyroid surgery
* Congestive heart failure
* Renal insufficiency
* Hepatic failure
* Current infection
* Treatment with steroids or anticoagulants
* Thyroid associated orbitopathy CAS \> 2
* Diabetes mellitus type 1
* Active cancer
* Severe psychiatric illness
* Amiodarone treatment
* Pregnancy
* Breast feeding
* Women of child bearing potential not using contraceptive
* Inability to comprehend the meaning of the study
* Iodine hypersensitivity

Primary outcomes:
measure: Temporary hypoparathyroidism
timeFrame: 1 month postoperatively
Secondary outcomes:
measure: Temporary laryngeal nerve palsy
timeFrame: 1 month postoperatively
measure: Permanent laryngeal nerve palsy
timeFrame: 6 months postoperatively
measure: Permanent hypoparathyroidism
timeFrame: 6 months postoperatively
Other outcomes:
measure: Change from Baseline in Quality of Life on the Thyroid Specific Patient Reported Outcome 39 (ThyPRO 29) questionnaire
timeFrame: 6 months postoperatively
Locations:
city: Solna
country: Sweden
facility: Department of Endocrinology, Karolinska University Hospital
state: Stockholm
Study officials:
affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet
name: Jan Calissendorff, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, Walter MA. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct;26(10):1343-1421. doi: 10.1089/thy.2016.0229.
citation: Kaur S, Parr JH, Ramsay ID, Hennebry TM, Jarvis KJ, Lester E. Effect of preoperative iodine in patients with Graves' disease controlled with antithyroid drugs and thyroxine. Ann R Coll Surg Engl. 1988 May;70(3):123-7.
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citation: Yilmaz Y, Kamer KE, Ureyen O, Sari E, Acar T, Karahalli O. The effect of preoperative Lugol's iodine on intraoperative bleeding in patients with hyperthyroidism. Ann Med Surg (Lond). 2016 Jun 16;9:53-7. doi: 10.1016/j.amsu.2016.06.002. eCollection 2016 Aug.
citation: Huang SM, Liao WT, Lin CF, Sun HS, Chow NH. Effectiveness and Mechanism of Preoperative Lugol Solution for Reducing Thyroid Blood Flow in Patients with Euthyroid Graves' Disease. World J Surg. 2016 Mar;40(3):505-9. doi: 10.1007/s00268-015-3298-8.
citation: Calissendorff J, Falhammar H. Rescue pre-operative treatment with Lugol's solution in uncontrolled Graves' disease. Endocr Connect. 2017 May;6(4):200-205. doi: 10.1530/EC-17-0025. Epub 2017 Mar 21.
citation: Calissendorff J, Falhammar H. Lugol's solution and other iodide preparations: perspectives and research directions in Graves' disease. Endocrine. 2017 Dec;58(3):467-473. doi: 10.1007/s12020-017-1461-8. Epub 2017 Oct 26.
citation: Spallek L, Krille L, Reiners C, Schneider R, Yamashita S, Zeeb H. Adverse effects of iodine thyroid blocking: a systematic review. Radiat Prot Dosimetry. 2012 Jul;150(3):267-77. doi: 10.1093/rpd/ncr400. Epub 2011 Oct 20.
citation: Nauman J, Wolff J. Iodide prophylaxis in Poland after the Chernobyl reactor accident: benefits and risks. Am J Med. 1993 May;94(5):524-532. doi: 10.1016/0002-9343(93)90089-8. No abstract available.