Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT06222606 |
Other study ID # |
1-10-72-120-23 |
Secondary ID |
|
Status |
Recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
January 2024 |
Est. completion date |
January 2026 |
Study information
Verified date |
January 2024 |
Source |
Aarhus University Hospital |
Contact |
Jacob Kinggaard Lilja-Fischer, MD |
Phone |
+4540460399 |
Email |
jaclil[@]rm.dk |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The study aims to test if use of autofluorescence imaging (AF) reduces the risk of developing
hypoparathyroidism (hypoPT) following surgery for thyroid cancer, either total thyroidectomy
(TT) or completion hemithyroidectomy (cHT).
Description:
Purpose The study aims to test if use of autofluorescence imaging (AF) reduces the risk of
developing hypoparathyroidism (hypoPT) following surgery for thyroid cancer, either total
thyroidectomy (TT) or completion hemithyroidectomy (cHT).
Background The mainstay of treatment of thyroid cancer is surgery. Many patients will need
only surgery with removal of one half of their thyroid gland, a hemithyroidectomy (HT), while
others will need to have all of the thyroid gland removed.1 This may be done in one
procedure, a total thyroidectomy (TT), or in two procedures with a completion
hemithyroidectomy (cHT) after an initial HT. The indication for complete removal of the
thyroid gland, may be to remove all cancer tissue, to facilitate adjuvant treatment with
radioactive iodine, or both.
Following adequate treatment, overall prognosis is very favorable, with a 3-year overall
survival of 98% for all Danish patients diagnosed in 2018.2 Thus, a major point of attention
is to minimize treatment-related morbidity, and enable cancer survivorship with as few
late-effects as possible.
Surgery for thyroid cancer comes with general surgical risks of bleeding and infection, and
specific for thyroid surgery is the risk of injury to nerves to the larynx, which is
relatively rare, below 5%. Hypothyroidism is obligatory after TT/cHT, and is seen in 10-15%
after HT.
Specific to patients after TT/cHT is damage to the parathyroid glands (PGs), which leads to
hypoparathyroidism (hypoPT).
HypoPT is generally thought to be an avoidable surgical complication, but nonetheless it is
relatively frequent after surgery for thyroid cancer, depending on the definition applied.3-5
Only patients who have a TT or cHT are at risk of developing hypoPT, since the two
contralateral PGs will not have been disturbed and HT is generally not associated with
hypoPT.
HypoPT may be transient, but is often permanent. Chronic hypoPT leads to lifelong need for
medical surveillance and treatment, and is often difficult to treat. It comes with a risk of
health complications (renal and neuropsychiatric), is frequently symptomatic (often cognitive
and neuromuscular), and leads to decreased quality of life.6 Thus, there is a need to
decrease the risk of hypoPT after surgery for thyroid cancer. Further, due to the favorable
prognosis and relatively young age of patients, any improvement will lead to a substantial
gain in years lived without complications for each patient, and decreased medical spending
for society as a whole. Recently, the national guidelines have been revised to reduce the
number of patients who will need TT/cHT and thus be at risk of hypoPT, but still there is a
substantial burden of morbidity that needs to be reduced.
Avoidance of hypoPT mainly lies with the surgeon's experience and skills, since
identification and preservation of PGs may be very difficult, due to their small size and
delicate structure. Identification of PGs is visual, and depends on the surgeon's knowledge
of their usual position in relation to the thyroid gland. In the setting of advanced thyroid
cancer, preservation of PGs may be extremely difficult, since removal of the primary tumor
and metastases adjacent to the PGs is the overwhelming priority.
Recently, it has been discovered that PGs possess unique autofluorescent properties, in that
the tissue will return light in a specific wavelength after illumination with infrared light
of a specific wavelength. This autofluorescence (AF) may be observed with a hand-held camera
system during surgery, allowing the surgeon to more easily visualize and identify PGs.7 This
could potentially lead to improved preservation of PGs, and thus decreased risk of hypoPT.
Study design The planned trial is a randomized, controlled superiority trial with two
parallel arms. The investigators seek to include patients undergoing surgery for thyroid
cancer, who are at risk of developing hypoPT as a complication to surgery. Patients will be
randomized 1:1 to surgery with or without the added use of AF during surgery.
Study setting and practical conduct The trial is to be conducted at Aarhus University
Hospital, in a collaboration between Department of Otorhinolaryngology - Head & Neck Surgery
and Department of Endocrinology. Here, approximately 100 patients undergo surgery for thyroid
cancer annually. A further 4-500 patients have thyroid surgery for benign disease, and
another approximately 300 patients have surgery for parathyroid disease. Thus, there is a
steady high flow of eligible patients, and the hospital as well as the treating surgeons are
highly qualified to undertake this study. Autofluorescence imaging with the EleVision IR
system is available, and is used ad hoc for thyroid and parathyroid surgery.
Patient flow Patients referred on suspicion of thyroid cancer to the Head and Neck Surgery
Clinic at Aarhus University Hospital will be considered for inclusion in the trial.
Approximately half of patients with thyroid cancer will need TT or cHT, and will thus be
eligible for the trial. The investigators aim to include 110 patients, which should be
achievable in approximately two years.
Randomization Following patient consent, an electronic case file will be created in the
REDCap electronic data capture tool. Randomization is performed electronically in the
dedicated REDCap randomization module.
Randomization will be stratified by TT or cHT.
Intervention Patients randomized to the experimental group will have surgery performed in the
exact same manner as in the control group.
In the experimental group, the surgeon will use the EleVision IR camera system (Medtronic,
USA) to visualize PGs during surgery. The surgeon will use AF at minimum two timepoints on
each side of the neck: First, when the thyroid lobe is exposed and mobilized, and secondly
after removal of the thyroid lobe. This is repeated in the contralateral side of the neck in
case of TT. If a central neck dissection is performed, the specimen is also examined with AF
following removal. Autotransplantation of inadvertently removed PGs may be performed after
frozen section histology.
Endpoints HypoPT following surgery is defined as hypocalcemia (ionized plasma calcium levels
below lower limit of reference, 1,18 mmol/l), with inappropriately low plasma levels of PTH
(assessed by 2 separate measurements) necessitating treatment with active vitamin D, as
determined by the treating physician.
Deviation from standard treatment All patients, whether randomized to standard or
experimental treatment arm, will receive treatment according to national clinical guidelines
published by the Danish Thyroid Cancer Group (DATHYRCA).1 The extent of surgery will be
exactly the same in either group, and will not deviate from standard treatment.
Sample size The investigators estimate that the rate of hypoPT requiring medical treatment in
the control group will be approximately 30%. A reduction to 10% will be clinically
significant, and statistically significant at α=0.05 with a power of β=0.8 with inclusion of
98 patients. To allow for dropouts, the investigators aim to include 110 patients, which
should be achievable in approximately two years.
Interim analysis The investigators plan to perform an interim analysis after inclusion of 50
patients with available data on the primary endpoint. The trial may be terminated if the
investigators are able to show that it would be highly unlikely to reach the primary
endpoint. This may be due to no effect of the intervention, or a lower than expected risk of
hypoPT in the control group. Both scenarios would make it highly unlikely to reach the
primary endpoint of the study.
Statistical analysis plan For the primary endpoint, relative risk for hypoPT will be
calculated along with its associated 95% confidence interval, and a p-value will be
calculated from a chi2-test. The investigators will provide a crude estimate, as well as
adjusted for operating surgeon, or suspicion of lymph node metastases on imaging and/or
planned neck dissection.
For secondary endpoints, a similar analysis will be performed for categorical data (Permanent
hypoPT; extent of surgery; complications). Continuous data (ioPTH reduction, time to
resolution of hypoPT, number of days hospitalized) will be described and analysed using a
t-test, or ranksum test in case of non-normal data. Survival endpoints will be described by a
hazard ratio with 95% confidence interval.
Patient characteristics, including demographics, disease status and treatment will be
characterized using descriptive statistics only.
Risk, side effects and disadvantages Use of AF during surgery involves nothing but 2 to 5
minutes of illumination of the surgical field with infrared light through a hand-held camera,
which displays an image on a monitor in which the infrared wavelengths are converted to
wavelengths visual to the human eye. The potential effect of use of AF in thyroid cancer
surgery is to make the surgeon more aware of the PGs, and thus incite the surgeon to change
his/her strategy in a more patient-safe direction.
Illumination of the surgical field with infrared light has no biological effect, cannot be
felt, and poses no danger to the patient. Thus, the intervention should not lead to
discomfort or pain, has no known side effects and would not pose a risk to the patient.