AzTrials
AzTrials

HyperthyroidismPhase 3NCT04856488

Preoperative Lugol's Solution in Graves' Disease and Toxic Nodular Goiter

A Phase 3 study testing Iodine-Potassium Iodide 5%-10% Oral and Topical Solution in people with Hyperthyroidism, run by Jan Calissendorff at 1 site in Sweden.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Hyperthyroidism
What is being tested?
Iodine-Potassium Iodide 5%-10% Oral and Topical Solution
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
182 participants
Where
1 siteSweden
Study dates
18 Nov 2021to Dec 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • Unstable coronary artery disease
  • Previous thyroid surgery
  • Congestive heart failure
  • Renal insufficiency
  • Hepatic failure
  • Current infection
Show all 17Show fewer
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jan Calissendorff, MD, PhD contact

+46(0)8 51770000

jan.calissendorff@regionstockholm.se

Fredric Hedberg, MD contact

+46(0)8 51770000

fredric.hedberg@regionstockholm.se

Sweden1 site, 1 recruiting

  • Department of Endocrinology, Karolinska University Hospital

    Solna, Stockholm County, 17176

    Jan Calissendorff, MD.PhD, 0046 (0)8 51770000, jan.calissendorff@regionstockholm.se

    Fredric Hedberg, MD, 0046 (0)8 51770000, fredric.hedberg@regionstockholm.se

    Recruiting

Other trials in Sweden

About this study

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

Read the 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.

Conditions
Hyperthyroidism
Being tested
Iodine-Potassium Iodide 5%-10% Oral and Topical Solution
Medical subject headings
Hyperthyroidism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Iodine-Potassium Iodide 5%-10% Oral and Topical SolutionDrug

    Also called Lugol's solution

    Iodine Potassium Iodide 5% oral solution, administered 3 times per day for 10 days

Study groups in NCT04856488
Study groupRoleWhat they receive
Iodine Potassium Iodide solutionExperimentalParticipants receive Iodine Potassium Iodide solution oral drops 3 times per day for 10 Days prior to thyroidectomy in addition to standard preoperative treatment
Receives: Drug: Iodine-Potassium Iodide 5%-10% Oral and Topical Solution
No interventionNo interventionParticipants continue with standard preoperative treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Temporary hypoparathyroidism

    Numbers of participants with signs of hypoparathyroidism measured as hypocalcemia, low parathormone (PTH), supplementation with per oral vitamin D or calcium.

    Measured: 1 month postoperatively

Secondary outcomes (3)

  1. Temporary laryngeal nerve palsy

    Number of patients with postoperative signs of vocal chord damage via clinical assessment or laryngoscopy.

    Measured: 1 month postoperatively

  2. Permanent laryngeal nerve palsy

    Number of patients with postoperative signs of vocal chord damage via clinical assessment or laryngoscopy.

    Measured: 6 months postoperatively

  3. Permanent hypoparathyroidism

    Numbers of participants with signs of hypoparathyroidism measured as hypocalcemia, low PTH, supplementation with per oral vitamin D or calcium.

    Measured: 6 months postoperatively

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Apr 2021
  2. Study start18 Nov 2021
  3. Primary completionAug 2028 (estimated)
  4. Study completionDec 2028 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
182 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04856488
Sponsor's protocol ID
LugolProtocol001
Status last verified
Feb 2026
First submitted
6 Apr 2021
Last updated
10 Feb 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The original contributions presented in the study are included in the article/supplementary material.

Publications

  • 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.

    PubMed 27521067

  • 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.

    PubMed 2457351

  • Randle RW, Bates MF, Long KL, Pitt SC, Schneider DF, Sippel RS. Impact of potassium iodide on thyroidectomy for Graves' disease: Implications for safety and operative difficulty. Surgery. 2018 Jan;163(1):68-72. doi: 10.1016/j.surg.2017.03.030. Epub 2017 Nov 3.

    PubMed 29108701

  • Whalen G, Sullivan M, Maranda L, Quinlan R, Larkin A. Randomized trial of a short course of preoperative potassium iodide in patients undergoing thyroidectomy for Graves' disease. Am J Surg. 2017 Apr;213(4):805-809. doi: 10.1016/j.amjsurg.2016.07.015. Epub 2016 Aug 4.

    PubMed 27769543

  • Marigold JH, Morgan AK, Earle DJ, Young AE, Croft DN. Lugol's iodine: its effect on thyroid blood flow in patients with thyrotoxicosis. Br J Surg. 1985 Jan;72(1):45-7. doi: 10.1002/bjs.1800720118.

    PubMed 3967130

  • 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.

    PubMed 27408715

  • 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.

    PubMed 26546192

  • 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.

    PubMed 28325735

  • 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.

    PubMed 29075974

  • 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.

    PubMed 22021061

  • 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.

    PubMed 8498398

  • Hedberg F, Cramon PK, Branstrom R, Falhammar H, Calissendorff J. Assessing the impact of short-term Lugol's solution on toxic nodular thyroid disease: a pre-post-intervention study. Front Endocrinol (Lausanne). 2024 Jul 25;15:1420154. doi: 10.3389/fendo.2024.1420154. eCollection 2024.

    PubMed 39119004

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Iodine-Potassium Iodide 5%-10% Oral and Topical Solution in people with Hyperthyroidism, run by Jan Calissendorff at 1 site in Sweden.

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 2 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jan Calissendorff, MD, PhD (+46(0)8 51770000, jan.calissendorff@regionstockholm.se), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Temporary hypoparathyroidism (time frame: 1 month postoperatively). 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 NCT04856488, which also lists 12 linked publications.

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 10 Feb 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in