Clinical trial NCT04080505
Conditions: Graves Disease
Sponsor: Columbia University
Start date: 2015-02-10; Completion date: 2023-03-03
Enrollment: 29 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this research is to find out if SSKI (Potassium Iodide) reduces vascularity (the number and concentration of blood vessels) and improves how well patients do after surgery for removal of their whole thyroid gland in Graves' disease (an autoimmune disease that is a common cause of hyperthyroidism).

Detailed description:
Patients with Graves' disease and goiters tend to have very vascular thyroid glands, which increases operative bleeding risks/rates. Many surgeons treat these patients with preoperative SSKI which is believed to decrease the vascularity, which in turn may decrease bleeding risks. However, there has been no quantitative data published on whether this is a real effect with true clinical benefit, in either animal or human models with SSKI. There have been some studies in Europe studying Lugol's solution, a different formulation of iodine, which show some decreased vascularity using color Doppler or measurements of CD34 cells.

Arms: arm 1: Participants randomized to receive 7 days of pre-operative SSKI arm 2: Participants randomized to not receive any drug pre-operative
Interventions: intervention 1: SSKI- Potassium Iodide
Intervention descriptions: intervention 1: 1g/mL, 2 drops orally 3 times a day for 7 days before surgery

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
 
 
 
Title: 
Does the Use of Pre-operative SSKI Actually Reduce Vascularity 
and Improve Surgical Outcomes for Total Thyroidectomy in 
Graves' Disease? 
 
ClinicalTrials.gov ID: NCT04080505 
 
Protocol date: February 23, 2015 
 
 


 
Research/Protocol Hypothesis 
We hypothesize that the pre-operative use of SSKI (potassium iodide oral solution) reduces the 
hypervascularity of the thyroid gland in Graves’ disease patients undergoing total thyroidectomy, 
thus reducing blood loss, operative time, and complications.  
Scientific Abstract 
Patients with Graves’ disease who undergo total thyroidectomy are often treated with a 7-14 day 
pre-operative course of SSKI. This concentrated solution of potassium iodide not only helps to 
convert patients from a hyperthyroid to euthyroid state, but also is thought to reduce the 
vascularity of the thyroid gland for surgery. However, there is no published literature evaluating 
whether there is a true quantitative decrease in vascularity with SSKI treatment. In this 
prospective, randomized study, we aim to quantify if there is any change in vascular flow with 
SSKI treatment and if this difference results in a clinically significant difference in surgical 
outcomes.  
Methods  
Patients will be randomized into two treatment groups – those who receive SSKI for 7 days 
before surgery and those who do not. To assess vascular flow within the thyroid gland, all 
patients will get a baseline neck ultrasound when evaluated in the office, as well as a second 
ultrasound in the operating room before surgery. Using 3D imaging software, we will quantify 
the vascular flow in the ultrasound images and compare baseline images with the OR images to 
assess if there is a difference in vascular flow between these timepoints. Other endpoints we will 
measure are: estimated blood loss in surgery, total operative time, postoperative complications 
including rates of recurrent laryngeal nerve injury, hypoparathyroidism, hematoma, infection 
rates.  
Study Description 
Study Purpose and Rationale  
Patients with Graves’ disease and goiters tend to have very vascular thyroid glands, which 
increases operative bleeding risks/rates. Many surgeons treat these patients with preoperative 
SSKI which is believed to decrease the vascularity, which in turn may decrease bleeding risks. 
However, there has been no quantitative data published on whether this is a real effect with true 
clinical benefit, in either animal or human models with SSKI. There have been some studies in 
Europe studying Lugol’s solution, a different formulation of iodine, which show some decreased 
vascularity using color Doppler or measurements of CD34 cells (1,2).  
Study Design & Procedures 
All patients would receive a baseline neck ultrasound on our initial office consultation. We do 
our own office ultrasounds to assess the pathology ourselves. In this study we would standardize 


all patients to have a baseline ultrasound with us to obtain vascular flow imaging no less than 7 
days prior to surgery. 
Patients would be randomized to either receive 7 days of pre-operative SSKI or not receive any 
drug (in our current practice at Columbia, all patients with Graves’ disease receive SSKI pre-
operatively, though this is not standard practice across the country, thus the ‘no drug’ group 
would be experimental for research). Prescriptions will be written by the surgeon and filled by 
the patient at an outside pharmacy.  
All patients would receive a second ultrasound on the operating table before surgery to assess for 
change in vascularity (experimental, as not all patients receive intra-operative ultrasounds before 
surgery). Both ultrasounds are performed by the surgeon and there is no additional charge for 
this test.  
We would record estimated blood loss, operative length, and other complication rates such as 
recurrent laryngeal nerve injury, hypoparathyroidism, hematoma, infection (these rates are 
already recorded for all patients).  
Any post-operative procedures and data collection will be standard of care. We will review 
consented patients’ chart if there are any post-op complications. If there are no complications, 
the data collection will be complete at their post-op appointment.  
Study Drugs or Devices  
SSKI is potassium iodide oral solution. It is a concentrated form of potassium iodide containing 
1g/ml. It is commonly used for lung conditions such as emphysema, bronchitis and works as an 
expectorant. It works by thinning mucous secretions (phlegm) in the lungs.  
Saturated solutions of potassium iodide can be used for hyperthyroidism or thyroid storm, as 
high amounts of iodide temporarily suppress secretion of thyroxine from the thyroid gland.  
Ultrasound will be used to take images of thyroid to measure thyroid volumes, as well as take 
images of the vascular flow in each lobe of the gland.  
Using 3D imaging software, we will quantify the vascular flow in the ultrasound images and 
compare baseline images with the OR images to assess if there is a difference in vascular flow 
between these timepoints. 
Study Subjects  
Inclusion criteria: All patients with Graves’ disease who will be undergoing total thyroidectomy.  
Exclusion criteria: Age less than 18, previous RAI therapy, previous treatment with SSKI.  
Our goal recruitment number for this pilot study is 30 patients. 
 
 


Statistical Analysis 
We believe that a decrease in vascularity of at least 10% would be clinically significant. In order 
to demonstrate this amount of difference, our pilot study would be adequately powered with at 
least 40 patients to show a difference of 11% between the two treatment arms. Utilizing the 
program “Power and Sample Size Calculation v 3.0.43”, a power analysis was conducted setting 
type I error at 0.05, Power at 0.8, and an experiment to control arm ratio of 2:1. In order to detect 
a clinically significant change of 10% vascularity in the gland, 20 patients will need to be 
included in the experimental arm and 10 patients in the control arm. 
References 
1. Erbil Y, Ozluk Y, Giriş M, et al. Effect of lugol solution on thyroid gland blood flow and 
microvessel density in the patients with Graves' disease. J Clin Endocrinol Metab. 2007 
Jun;92(6):2182-9.  
2. Ansaldo GL, Pretolesi F, Varaldo E, et al Doppler evaluation of intrathyroid arterial 
resistances during preoperative treatment with Lugol's iodide solution in patients with diffuse