Trial Outcomes & Findings for Central Neck Dissection in Patients With Clinical Node Negative Thyroid Cancer (NCT NCT02138214)

NCT ID: NCT02138214

Last Updated: 2020-12-21

Results Overview

Rate of transient hypoparathyroidism will be assessed in terms of percentage of participants with day 1 serum PTH level of \< 10 pg/ml.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 117 participants
• Primary outcome timeframe: Post-operative day 1
• Results posted on: 2020-12-21

Participant Flow

117 participants consented. 27 participants were excluded from the study before assignment to arms (15 participants withdrew before surgery, 12 participants did not meet intraoperative inclusion criteria). 90 participants were allocated in 3 arms

Participant milestones

Measure	Arm I (no CND) Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm II (CND) Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm III (SOC) Patients who are not eligible for randomization into Arm I or Arm II, Standard of Care (SOC) group. No specific trial intervention, treated as per patient and physician preference Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Overall Study STARTED	30	30	30
Overall Study Analyzed for Baseline Measures	30	29	30
Overall Study COMPLETED	30	26	26
Overall Study NOT COMPLETED	0	4	4

Reasons for withdrawal

Measure	Arm I (no CND) Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm II (CND) Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm III (SOC) Patients who are not eligible for randomization into Arm I or Arm II, Standard of Care (SOC) group. No specific trial intervention, treated as per patient and physician preference Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Overall Study Withdrawal by Subject	0	1	0
Overall Study Lost to Follow-up	0	2	4
Overall Study Screen Failure	0	1	0

Baseline Characteristics

Central Neck Dissection in Patients With Clinical Node Negative Thyroid Cancer

Baseline characteristics by cohort

Measure	Arm I (no CND) n=30 Participants Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm II (CND) n=29 Participants Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm III (SOC) n=30 Participants Patients who are not eligible for randomization into Arm I or Arm II, Standard of Care (SOC) group. No specific trial intervention, treated as per patient and physician preference Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Total n=89 Participants Total of all reporting groups
Age, Continuous	46.10 years STANDARD_DEVIATION 1.47 • n=5 Participants	50.07 years STANDARD_DEVIATION 2.38 • n=7 Participants	43.17 years STANDARD_DEVIATION 2.68 • n=5 Participants	46.40 years STANDARD_DEVIATION 1.47 • n=4 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	21 Participants n=7 Participants	27 Participants n=5 Participants	71 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	8 Participants n=7 Participants	3 Participants n=5 Participants	18 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants	29 Participants n=7 Participants	28 Participants n=5 Participants	86 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	28 Participants n=7 Participants	27 Participants n=5 Participants	85 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	30 participants n=5 Participants	29 participants n=7 Participants	30 participants n=5 Participants	89 participants n=4 Participants

PRIMARY outcome

Timeframe: Post-operative day 1

Population: 1 participant in the Arm II(CND) was a screen failure. Arm III(SOC) data was not collected for this outcome measure as outcome is a comparison of complication rates between TT and CND arms and does not apply to SOC arm participants. The SOC arm was added later as comparison for the qualitative aims only.

Rate of transient hypoparathyroidism will be assessed in terms of percentage of participants with day 1 serum PTH level of < 10 pg/ml.

Outcome measures

Measure	Arm II (CND) n=29 Participants Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm I (no CND) n=30 Participants Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Percentage of Participants With Transient Hypoparathyroidism, as Defined by a Day 1 Serum Parathyroid Hormone (PTH) Level of < 10 pg/ml	24.1 percentage of participants	33.3 percentage of participants

PRIMARY outcome

Timeframe: At day 12

Population: 1 participant in the Arm II(CND) was a screen failure. Arm III(SOC) data was not collected for this outcome measure as outcome is a comparison of complication rates between TT and CND arms and does not apply to SOC arm participants. The SOC arm was added later as comparison for the qualitative aims only.

Post-operative serum calcium (mg/dL) at Day 12

Outcome measures

Measure	Arm II (CND) n=29 Participants Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm I (no CND) n=30 Participants Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Post-operative Serum Calcium (mg/dL) at Day 12	9.39 mg/dL Standard Error 0.12	9.13 mg/dL Standard Error 0.1

PRIMARY outcome

Timeframe: 2 weeks after surgery

Population: 19 participants in CND arm, 22 in 'no CND' arm returned their calcium symptom log to study staff at the end of the postoperative follow-up period. Missing data is due to participants losing/forgetting to return their calcium symptom logs/lack of clarity in their handwritten log entries. This may also have led to limited reliability/accuracy of the data we were able to collect. SOC arm data was not collected as outcome is a comparison of complication rates between TT and CND arms, N/A to SOC arm.

Total calcium consumption in first 2 weeks (total mg). Participants were given calcium symptom logs in which to record their calcium consumption between surgery and their first preoperative follow up appointment, approximately two week.

Outcome measures

Measure	Arm II (CND) n=19 Participants Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm I (no CND) n=22 Participants Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Total Calcium Consumption in First 2 Weeks	21876.63 mg Standard Error 6353.42	25470.19 mg Standard Error 6592.60

PRIMARY outcome

Timeframe: 2 weeks

Population: In Arm II (CND) 1 participant was lost to screen failure, 1 self-withdrew. Arm III(SOC) data was not collected for this outcome measure as outcome is a comparison of complication rates between TT and CND arms and does not apply to SOC arm participants. The SOC arm was added later as comparison for the qualitative aims only.

Number of participants with hypocalcemia symptoms and symptom severity in first two weeks, as defined by presence of clinically significant symptoms of hypocalcemia.

Clinically significant symptoms defined as 1 or more episodes of symptoms of hypocalcemia per day for multiple days, symptoms leading to calls to provider for assistance with managing and/or symptoms leading to escalation of dosage of prescribed medications to treat symptoms of hypocalcemia

Outcome measures

Measure	Arm II (CND) n=28 Participants Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm I (no CND) n=30 Participants Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Number of Participants With Hypocalcemia Symptoms in First 2 Weeks	8 participants	6 participants

PRIMARY outcome

Timeframe: 2 weeks post surgery

Population: Missing data is due to participants losing/forgetting to return their calcium symptom logs/lack of clarity in their handwritten log entries. This may also have led to limited reliability/accuracy of the data we were able to collect. SOC arm data was not collected as outcome is a comparison of complication rates between TT and CND arms, not applicable (N/A) to SOC arm.

Mean number of occurrences of mild (severity 1 - 2) and severe (severity 3 - 5) hypocalcemia symptoms. Participants were asked to record hypocalcemia symptoms between surgery and first postoperative follow-up at approximately two weeks in their provided calcium symptom logs and rank severity on scale of 1 (mild) to 5 (severe).

Outcome measures

Measure	Arm II (CND) n=13 Participants Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm I (no CND) n=19 Participants Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Hypocalcemia Symptom Severity Scale (Range of 1-5) mild symptoms (severity 1 - 2)	3 occurrences Standard Error 1.49	2.50 occurrences Standard Error 0.81
Hypocalcemia Symptom Severity Scale (Range of 1-5) severe symptoms (severity 3 - 5)	3.36 occurrences Standard Error 1.59	1.42 occurrences Standard Error 0.73

PRIMARY outcome

Timeframe: At Month 6

Population: In Arm II (CND) 1 participant was lost to screen failure, 1 self-withdrew, 1 was lost to follow up. Arm III(SOC) data was not collected for this outcome measure as outcome is a comparison of complication rates between TT and CND arms and does not apply to SOC arm participants. The SOC arm was added later as comparison for the qualitative aims only.

Requirement for calcium and calcitriol at Month 6 (or, if laboratory values at visit reveal calcium < 8 mg/dL and PTH <15 pg/ml)

Outcome measures

Measure	Arm II (CND) n=27 Participants Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm I (no CND) n=30 Participants Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Percentage of Participants That Required Calcium and Calcitriol at Month 6	0 Participants	3 Participants

PRIMARY outcome

Timeframe: At Month 6

Population: In Arm II (CND) 1 participant was lost to screen failure, 1 self-withdrew, 1 was lost to follow up. Arm III(SOC) data was not collected for this outcome measure as outcome is a comparison of complication rates between TT and CND arms and does not apply to SOC arm participants. The SOC arm was added later as comparison for the qualitative aims only.

Outcome measures

Measure	Arm II (CND) n=27 Participants Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm I (no CND) n=30 Participants Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Post-operative Serum PTH (pg/ml) at Month 6	45.62 pg/mL Standard Error 4.6	44.24 pg/mL Standard Error 4.97

PRIMARY outcome

Timeframe: At Month 6

Population: In Arm II (CND) 1 participant was lost to screen failure, 1 self-withdrew, 1 was lost to follow up. Arm III(SOC) data was not collected for this outcome measure as outcome is a comparison of complication rates between TT and CND arms and does not apply to SOC arm participants. The SOC arm was added later as comparison for the qualitative aims only.

Post-operative serum calcium (mg/dL) at Month 6

Outcome measures

Measure	Arm II (CND) n=27 Participants Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm I (no CND) n=30 Participants Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Post-operative Serum Calcium Level at Month 6	9.12 mg/dL Standard Error 0.08	8.98 mg/dL Standard Error 0.13

SECONDARY outcome

Timeframe: Post-operative day 1 - Month 6

The rate of transient and permanent hypocalcemia will be determined by assessing the following:

I. Post-operative serum calcium (mg/dl) and PTH (pg/ml) at Day 12 and Month 6 II. Total calcium consumption in first 2 weeks (total gm) III. Hypocalcemia symptoms in first 2 weeks (average episodes/day) IV. Hypocalcemia symptom severity scale (range 1-5) V. Requirement for calcium and calcitriol at Month 6 (or, if laboratory values at visit reveal calcium < 8 mg/dL and PTH < 15 pg/ml

Data will be analyzed using the methods described above.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Post operative day 1 - up to 1 year

The rate of voice and swallowing problems will be determined by assessing the following:

I. Phonation threshold pressure, in centimeters of water II. Dysphonia severity index (DSI) score (+5 to -5) III. Grade Roughness Breathiness Asthenia Strain (GRBAS) score (0-3) IV. Voice quality parameters as measured by Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) (0-100 on visual analog scale) V. Vocal fold vibratory and movement parameters as measured by stroboscopy assessment (1-4) VI. Glottal function index score VII. Penetration-Aspiration score as measured by videofluoroscopic swallow study (0-8)

Data will be analyzed using the methods described above.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Post-operative day 1 - up to 1 year

The degree to which quality (QOL) is compromised will be determined by assessing the following:

I. Short Form Health Survey (SF-12) Mental Composite Scale (MCS) score II. Short Form Health Survey (SF-12) Physical Composite Scale (PCS) score III. European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core-30 (C30) score IV. Thyroid Cancer Specific Quality of Life (ThyCA-QOL) score V. 10-item Eating Assessment Tool (EAT-10) dysphagia inventory score VI. Voice Handicap Index (VHI) score VII. Themes and codes from interview transcripts assessed using qualitative research methods

Data will be analyzed using the methods described above.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 6 - up to 5 years

Clinical recurrence rates will be determined by assessing the following:

I. Percent of patients with a recombinant thyroid-stimulating hormone (rTSH) stimulated thyroglobulin level < 1 ng/ml one year after surgery II. Unstimulated thyroglobulin level prior to beginning week 6 radioactive iodine treatment III. Stimulated thyroglobulin at the time of week 6 radioactive iodine treatment IV. Incidence of unstimulated thyroglobulin > 1 ng/mL at 6 months V. Incidence of stimulated thyroglobulin > 2 ng/mL at 1 year VI. Incidence of biopsy-proven disease identification on neck ultrasound or iodine-131 (I-131) uptake up to 5 years post-surgery

Data will be analyzed using the methods described above.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Post-operative day 1 - up to 1 year

The degree to which accurate quality of life (QOL) measures can be extracted from patient interview narratives using natural language process techniques will allow for the development of computer algorithms that convert patient narrative text into simple quality of life measures. Data will be analyzed using the methods described above.

Outcome measures

Outcome data not reported

Adverse Events

Arm I (no CND)

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Arm II (CND)

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Arm III (SOC)

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Arm I (no CND) n=30 participants at risk Patients undergo total thyroidectomy alone. Thyroidectomy: Undergo total thyroidectomy Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm II (CND) n=29 participants at risk Patients undergo total thyroidectomy with ipsilateral prophylactic CND. Thyroidectomy: Undergo total thyroidectomy Central lymph node dissection: Undergo total thyroidectomy with ipsilateral prophylactic CND Quality-of-life assessment: Voice evaluation, interviews, ancillary studies	Arm III (SOC) n=30 participants at risk Patients who are not eligible for randomization into Arm I or Arm II, Standard of Care (SOC) group. No specific trial intervention, treated as per patient and physician preference Quality-of-life assessment: Voice evaluation, interviews, ancillary studies
Injury, poisoning and procedural complications biochemical hypopcalcemia	6.7% 2/30 • Number of events 2 • 1 year	0.00% 0/29 • 1 year	3.3% 1/30 • Number of events 1 • 1 year
Injury, poisoning and procedural complications symptomatic hypoparathyroidism	6.7% 2/30 • Number of events 2 • 1 year	13.8% 4/29 • Number of events 4 • 1 year	3.3% 1/30 • Number of events 1 • 1 year
Injury, poisoning and procedural complications nerve injury	40.0% 12/30 • Number of events 12 • 1 year	24.1% 7/29 • Number of events 7 • 1 year	10.0% 3/30 • Number of events 3 • 1 year
Injury, poisoning and procedural complications significant voice changes not otherwise characterized	36.7% 11/30 • Number of events 11 • 1 year	24.1% 7/29 • Number of events 7 • 1 year	6.7% 2/30 • Number of events 2 • 1 year
Injury, poisoning and procedural complications biochemical hypoparathyroidism	30.0% 9/30 • Number of events 9 • 1 year	27.6% 8/29 • Number of events 8 • 1 year	10.0% 3/30 • Number of events 3 • 1 year
Injury, poisoning and procedural complications symptomatic hypocalcemia	13.3% 4/30 • Number of events 4 • 1 year	20.7% 6/29 • Number of events 6 • 1 year	6.7% 2/30 • Number of events 2 • 1 year

Additional Information

Dr. Rebecca Sippel

University of Wisconsin, Madison

Phone: 608-263-1387

Email: sippel@surgery.wisc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place