Autofluorescence and Indocyanine Green to Avoid Hypocalcemia After Thyroidectomy

NCT05117853 | Recruiting Phase 3 DMC

• 1 other identifier: B1262021000021
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

• Hypoparathyroidism (and the resulting hypocalcemia) remains the most common morbidity after a total thyroidectomy.
• The identification and preservation of parathyroid glands during neck surgery has always been challenging but is crucial to avoid postoperative hypocalcemia.
• Recently, the specific autofluorescent characteristics of endogenous fluorophores in the parathyroid tissue have been used to detect and confirm parathyroid glands during thyroid surgery.
• Injecting indocyanine green and using its fluorescent characteristics has the advantage of adding information about the vascular supply of the parathyroid glands.
• This randomized clinical trial aims to investigate whether using autofluorescence and indocyanine green during thyroid surgery can predict or prevent postoperative hypocalcemia.

Conditions

Thyroid Disease; Hypoparathyroidism Postprocedural

Outcome Measures

Primary Outcomes (1)

• Postoperative hypocalcemia

  Defined as parathyroid hormone (PTH) levels \<15 pg/mL, serum calcium levels \<2.10 mmol/L, or the intake of calcium or activated vitamin D supplements after total thyroidectomy.

  One week after surgery

Secondary Outcomes (3)

• The number of identified parathyroid glands

  1 hour after surgery

• The number of reimplanted parathyroid glands

  1 hour after surgery

• The presence of late or permanent hypocalcemia

  Six months after surgery

Study Arms (2)

Autofluorescent detection and injection of indocyanine green

EXPERIMENTAL

Drug: indocyanine green (ICG) Autofluorescence detection of the parathyroid glands and injection of indocyanine green at two predefined timepoints will be performed to evaluate the vascularization of the parathyroid glands.

Drug: Autofluorescent detection + Injection of indocyanine green

Control group

PLACEBO COMPARATOR

Gold standard of visual identification and evaluation of viability.

Procedure: Gold standard of visual identification and evaluation of viability of the parathyroid glands.

Interventions

Autofluorescent detection + Injection of indocyanine green DRUG

All four parathyroid glands will be actively sought for in every case selected for the use of AF/ICG, with AF verification of parathyroid tissue. The timepoints of AF will be: * 1 = after lateral dissection side 1 (side 1) * 2= after lateral dissection side 2 (side 2) The timepoints of ICG injection will be: * 1 = after the first thyroid lobectomy (side 1) * 2 = after the second thyroid lobectomy (side 2) Scoring of the viability of parathyroid glands (adapted from Vidal Fortuny et al., 2016): * 1 = black = not viable/vascularized * 2 = grey = moderately viably/ moderately vascularized * 3 = white = viable/well-vascularized

Also known as: ICG Injection

Autofluorescent detection and injection of indocyanine green

Gold standard of visual identification and evaluation of viability of the parathyroid glands. PROCEDURE

Gold standard of visual identification and evaluation of viability of the parathyroid glands.

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All adult patients undergoing a total thyroidectomy without previous neck surgery.

You may not qualify if:

• Children and teenagers (\<18 years old)
• Patients refusing participation or unable/unwilling to sign the informed consent
• Patients with a completion thyroidectomy
• Patients with planned central and lateral neck lymph node dissections (thyroid cancer)
• Patients with previous neck surgery
• Patients with a known allergy/hypersensitivity to indocyanine green

Sponsors & Collaborators

• Onze Lieve Vrouw Hospital: lead

Study Sites (1)

Onze Lieve Vrouw Hospital

Aalst, 9300, Belgium

RECRUITING

Related Publications (22)

• Sitges-Serra A. Etiology and Diagnosis of Permanent Hypoparathyroidism after Total Thyroidectomy. J Clin Med. 2021 Feb 2;10(3):543. doi: 10.3390/jcm10030543.

  PMID: 33540657 BACKGROUND

• Moten AS, Thibault DP, Willis AW, Willis AI. Demographics, disparities, and outcomes in substernal goiters in the United States. Am J Surg. 2016 Apr;211(4):703-9. doi: 10.1016/j.amjsurg.2015.11.022. Epub 2016 Jan 6.

  PMID: 26813846 BACKGROUND

• Edafe O, Antakia R, Laskar N, Uttley L, Balasubramanian SP. Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia. Br J Surg. 2014 Mar;101(4):307-20. doi: 10.1002/bjs.9384. Epub 2014 Jan 9.

  PMID: 24402815 BACKGROUND

• Lorente-Poch L, Sancho JJ, Munoz-Nova JL, Sanchez-Velazquez P, Sitges-Serra A. Defining the syndromes of parathyroid failure after total thyroidectomy. Gland Surg. 2015 Feb;4(1):82-90. doi: 10.3978/j.issn.2227-684X.2014.12.04.

  PMID: 25713783 BACKGROUND

• Van Slycke S, Van Den Heede K, Bruggeman N, Vermeersch H, Brusselaers N. Risk factors for postoperative morbidity after thyroid surgery in a PROSPECTIVE cohort of 1500 patients. Int J Surg. 2021 Apr;88:105922. doi: 10.1016/j.ijsu.2021.105922. Epub 2021 Mar 25.

  PMID: 33774174 BACKGROUND

• Van Den Heede K, Tolley NS, Di Marco AN, Palazzo FF. Differentiated Thyroid Cancer: A Health Economic Review. Cancers (Basel). 2021 May 7;13(9):2253. doi: 10.3390/cancers13092253.

  PMID: 34067214 BACKGROUND

• Eismontas V, Slepavicius A, Janusonis V, Zeromskas P, Beisa V, Strupas K, Dambrauskas Z, Gulbinas A, Martinkenas A. Predictors of postoperative hypocalcemia occurring after a total thyroidectomy: results of prospective multicenter study. BMC Surg. 2018 Aug 9;18(1):55. doi: 10.1186/s12893-018-0387-2.

  PMID: 30092793 BACKGROUND

• Ji YB, Song CM, Sung ES, Jeong JH, Lee CB, Tae K. Postoperative Hypoparathyroidism and the Viability of the Parathyroid Glands During Thyroidectomy. Clin Exp Otorhinolaryngol. 2017 Sep;10(3):265-271. doi: 10.21053/ceo.2016.00724. Epub 2016 Aug 13.

  PMID: 27515510 BACKGROUND

• Van Slycke S, Van Den Heede K, Brusselaers N, Vermeersch H. Feasibility of Autofluorescence for Parathyroid Glands During Thyroid Surgery and the Risk of Hypocalcemia: First Results in Belgium and Review of the Literature. Surg Innov. 2021 Aug;28(4):409-418. doi: 10.1177/1553350620980263. Epub 2020 Dec 29.

  PMID: 33372584 BACKGROUND

• Benmiloud F, Godiris-Petit G, Gras R, Gillot JC, Turrin N, Penaranda G, Noullet S, Chereau N, Gaudart J, Chiche L, Rebaudet S. Association of Autofluorescence-Based Detection of the Parathyroid Glands During Total Thyroidectomy With Postoperative Hypocalcemia Risk: Results of the PARAFLUO Multicenter Randomized Clinical Trial. JAMA Surg. 2020 Feb 1;155(2):106-112. doi: 10.1001/jamasurg.2019.4613.

  PMID: 31693081 BACKGROUND

• Spartalis E, Ntokos G, Georgiou K, Zografos G, Tsourouflis G, Dimitroulis D, Nikiteas NI. Intraoperative Indocyanine Green (ICG) Angiography for the Identification of the Parathyroid Glands: Current Evidence and Future Perspectives. In Vivo. 2020 Jan-Feb;34(1):23-32. doi: 10.21873/invivo.11741.

  PMID: 31882459 BACKGROUND

• Riley RD, Moons KGM, Snell KIE, Ensor J, Hooft L, Altman DG, Hayden J, Collins GS, Debray TPA. A guide to systematic review and meta-analysis of prognostic factor studies. BMJ. 2019 Jan 30;364:k4597. doi: 10.1136/bmj.k4597. No abstract available.

  PMID: 30700442 BACKGROUND

• Alander JT, Kaartinen I, Laakso A, Patila T, Spillmann T, Tuchin VV, Venermo M, Valisuo P. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging. 2012;2012:940585. doi: 10.1155/2012/940585. Epub 2012 Apr 22.

  PMID: 22577366 BACKGROUND

• Reinhart MB, Huntington CR, Blair LJ, Heniford BT, Augenstein VA. Indocyanine Green: Historical Context, Current Applications, and Future Considerations. Surg Innov. 2016 Apr;23(2):166-75. doi: 10.1177/1553350615604053. Epub 2015 Sep 10.

  PMID: 26359355 BACKGROUND

• Obana A, Miki T, Hayashi K, Takeda M, Kawamura A, Mutoh T, Harino S, Fukushima I, Komatsu H, Takaku Y, et al. Survey of complications of indocyanine green angiography in Japan. Am J Ophthalmol. 1994 Dec 15;118(6):749-53. doi: 10.1016/s0002-9394(14)72554-1.

  PMID: 7977601 BACKGROUND

• Desmettre T, Devoisselle JM, Mordon S. Fluorescence properties and metabolic features of indocyanine green (ICG) as related to angiography. Surv Ophthalmol. 2000 Jul-Aug;45(1):15-27. doi: 10.1016/s0039-6257(00)00123-5.

  PMID: 10946079 BACKGROUND

• Vidal Fortuny J, Belfontali V, Sadowski SM, Karenovics W, Guigard S, Triponez F. Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery. Br J Surg. 2016 Apr;103(5):537-43. doi: 10.1002/bjs.10101. Epub 2016 Feb 11.

  PMID: 26864909 BACKGROUND

• Mirallie E, Borel F, Tresallet C, Hamy A, Mathonnet M, Lifante JC, Brunaud L, Menegaux F, Hardouin JB, Blanchard C; THYRQOL Group; Ansquer C, Mourrain-Langlois E, Delemazure AS, Perrot B, Longhi M, Nomine C, Espitalier F, Drui D, Caillard C, Renaud-Moreau N, Marret O, Mucci S, Christou N. Impact of total thyroidectomy on quality of life at 6 months: the prospective ThyrQoL multicentre trial. Eur J Endocrinol. 2020 Feb;182(2):195-205. doi: 10.1530/EJE-19-0587.

  PMID: 31804967 BACKGROUND

• Watt T, Cramon P, Hegedus L, Bjorner JB, Bonnema SJ, Rasmussen AK, Feldt-Rasmussen U, Groenvold M. The thyroid-related quality of life measure ThyPRO has good responsiveness and ability to detect relevant treatment effects. J Clin Endocrinol Metab. 2014 Oct;99(10):3708-17. doi: 10.1210/jc.2014-1322. Epub 2014 Jul 8.

  PMID: 25004246 BACKGROUND

• Chen Z, Zhao Q, Du J, Wang Y, Han R, Xu C, Chen X, Shu M. Risk factors for postoperative hypocalcaemia after thyroidectomy: A systematic review and meta-analysis. J Int Med Res. 2021 Mar;49(3):300060521996911. doi: 10.1177/0300060521996911.

  PMID: 33779362 BACKGROUND

• Kim J, Shin W. How to do random allocation (randomization). Clin Orthop Surg. 2014 Mar;6(1):103-9. doi: 10.4055/cios.2014.6.1.103. Epub 2014 Feb 14.

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  PMID: 29707253 BACKGROUND

MeSH Terms

Conditions

Thyroid Diseases

Condition Hierarchy (Ancestors)

Endocrine System Diseases

Central Study Contacts

Klaas Van Den Heede, MD

CONTACT

0032472893861; klaasvandenheede@hotmail.com

Sam Van Slycke, MD, PhD

CONTACT

003253724506; sam.van.slycke@olvz-aalst.be

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Simple blind (Only participant)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator / Scientific Fellow

Model Details: Single-center, comparative, randomized, single-blind, controlled trial against the gold standard of visual identification and viability evaluation.

Study Record Dates

• First Submitted: October 21, 2021
• First Posted: November 11, 2021
• Study Start: November 1, 2021
• Primary Completion: October 31, 2024
• Study Completion: May 31, 2025
• Last Updated: April 5, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available from 1 year after till 20 years after final study completion.
• Access Criteria: Data access request will be reviewed by the ethics committee of the Onze Lieve Vrouw Hospital, Aalst. Any request will require signing and completing a data access agreement.

Locations

BE (1)