Nitroglycerin for Intra-arterial Chemotherapy in Pediatric Retinoblastoma.

NCT04564521 | Unknown

• 1 other identifier: 2006-108-1134
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study is to evaluate the effect of intravenously infused nitroglycerin on the incidence of the cardio-respiratory side effects during the intra-arterial chemotherapy for retinoblastoma in pediatric patients. The intra-arterial chemotherapy at the ophthalmic artery is an important treatment option for retinoblastoma. However, the cardio-respiratory side effects (sudden onset of bradycardia, hypotension, a severe decrease in the compliance of lung, hypoxia) occasionally occurs during catheter manipulation in the ophthalmic artery. One of the purported mechanisms of cardio-respiratory side effects is vagal activation from the activation of trigeminal ganglion by afferent signals from the ophthalmic artery. Additionally, the chemotherapy agent can cause intra-arterial retinal precipitates. Therefore, it is expected that the dilation of the retinal artery may reduce the cardio-respiratory side effects and intra-arterial retinal precipitates. The hypothesis of this study is that the intravenously infused nitroglycerin will increase the compliance of the ophthalmic and retinal artery and decrease vagal stimulation and cardio-respiratory side effects during catheter manipulation and chemotherapy agent infusion. This is a single-center, double-blind, randomized, placebo-controlled study comparing the effect of intravenously infused nitroglycerin and saline on the incidence of the cardio-respiratory side effect in pediatric retinoblastoma patients undergoing intra-arterial chemotherapy. Prior to the procedure, each patient will be randomized into either the control-first arm, saline, or study-first arm, nitroglycerin.

Conditions

Retinoblastoma

Keywords

Intra-arterial chemotherapy; Cardio-respiratory side effects; Nitroglycerin

Outcome Measures

Primary Outcomes (1)

• The incidence of the cardio-respiratory side effects during ophthalmic artery selection and intra-arterial injection of chemotherapy agents. (percent)

  Bradycardia (\< 80% of Baseline), Hypotension (\< 80% of Baseline), Decrease in the lung compliance, Abnormal end-tidal CO2 curve, or Desaturation (SpO2 \<95%)

  During the intra-arterial chemotherapy (up to 4 hour)

Secondary Outcomes (9)

• The duration of the cardio-respiratory side effects during ophthalmic artery selection and intra-arterial injection of chemotherapy agents. (percent)

  During and after the intra-arterial chemotherapy (up to 48 hour)

• The incidence of using vaso-active drugs (percent)

  During and after the intra-arterial chemotherapy (up to 48 hour)

• The incidence of the side effect of nitroglycerin infusion (percent)

  During the intra-arterial chemotherapy (up to 4 hour)

• The concentration of inhaled sevoflurane (vol%)

  During the intra-arterial chemotherapy (up to 4 hour)

• The depth of anesthesia

  During the intra-arterial chemotherapy (up to 4 hour)

Study Arms (2)

Nitroglycerin

EXPERIMENTAL

Intravenous nitroglycerin (0.5mcg/kg/min) is infused after the induction of general anesthesia and during intra-arterial chemotherapy.

Drug: Nitroglycerin

Normal saline

ACTIVE COMPARATOR

Normal saline is infused after the induction of general anesthesia and during intra-arterial chemotherapy.

Drug: Normal saline

Interventions

Nitroglycerin DRUG

Intravenous nitroglycerin (0.5mcg/kg/min) is infused after the induction of general anesthesia and during intra-arterial chemotherapy to reduce the cardio-respiratory side effects.

Also known as: Intravenous nitroglycerin

Nitroglycerin

Normal saline DRUG

Intravenous normal saline is infused after the induction of general anesthesia and during intra-arterial chemotherapy as an active comparator.

Also known as: Intravenous normal saline

Normal saline

Eligibility Criteria

• Age: Up to 7 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Retinoblastoma patients who need intra-arterial chemotherapy under general anesthesia
• Residual intra-arterial chemotherapy ≥ 2 times (cross-over design)

You may not qualify if:

• Respiratory disease causing a decrease in lung compliance
• Unstable vital sign, significant arrhythmia or hypotension, Shock
• Hypersensitivity or contraindication to nitroglycerin
• Increased intracranial pressure, Intracranial hemorrhage
• Recent use of PDE5 inhibitors (\<24 hours after sildenafil or vardenafil; \<48 hours after tadalafil)

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Jin-Tae Kim

Seoul, South Korea

RECRUITING

Related Publications (11)

• FRAYSER R, HICKAM JB. EFFECT OF VASODILATOR DRUGS ON THE RETINAL BLOOD FLOW IN MAN. Arch Ophthalmol. 1965 May;73:640-2. doi: 10.1001/archopht.1965.00970030642008. No abstract available.

  PMID: 14281979 BACKGROUND

• Yaster M, Simmons RS, Tolo VT, Pepple JM, Wetzel RC, Rogers MC. A comparison of nitroglycerin and nitroprusside for inducing hypotension in children: a double-blind study. Anesthesiology. 1986 Aug;65(2):175-9. doi: 10.1097/00000542-198608000-00008.

  PMID: 3090906 BACKGROUND

• Dorner GT, Garhofer G, Kiss B, Polska E, Polak K, Riva CE, Schmetterer L. Nitric oxide regulates retinal vascular tone in humans. Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H631-6. doi: 10.1152/ajpheart.00111.2003. Epub 2003 May 15.

  PMID: 12750062 BACKGROUND

• Munier FL, Beck-Popovic M, Balmer A, Gaillard MC, Bovey E, Binaghi S. Occurrence of sectoral choroidal occlusive vasculopathy and retinal arteriolar embolization after superselective ophthalmic artery chemotherapy for advanced intraocular retinoblastoma. Retina. 2011 Mar;31(3):566-73. doi: 10.1097/IAE.0b013e318203c101.

  PMID: 21273941 BACKGROUND

• Shields CL, Bianciotto CG, Jabbour P, Ramasubramanian A, Lally SE, Griffin GC, Rosenwasser R, Shields JA. Intra-arterial chemotherapy for retinoblastoma: report No. 1, control of retinal tumors, subretinal seeds, and vitreous seeds. Arch Ophthalmol. 2011 Nov;129(11):1399-406. doi: 10.1001/archophthalmol.2011.150. Epub 2011 Jun 13.

  PMID: 21670328 BACKGROUND

• Shields CL, Bianciotto CG, Jabbour P, Griffin GC, Ramasubramanian A, Rosenwasser R, Shields JA. Intra-arterial chemotherapy for retinoblastoma: report No. 2, treatment complications. Arch Ophthalmol. 2011 Nov;129(11):1407-15. doi: 10.1001/archophthalmol.2011.151. Epub 2011 Jun 13.

  PMID: 21670326 BACKGROUND

• Fallaha N, Dubois J, Carret AS, Callejo SA, Hamel P, Superstein R. Real-time ophthalmoscopic findings of intraophthalmic artery chemotherapy in retinoblastoma. Arch Ophthalmol. 2012 Aug;130(8):1075-7. doi: 10.1001/archophthalmol.2012.180. No abstract available.

  PMID: 22893086 BACKGROUND

• Cugati S, Varma DD, Chen CS, Lee AW. Treatment options for central retinal artery occlusion. Curr Treat Options Neurol. 2013 Feb;15(1):63-77. doi: 10.1007/s11940-012-0202-9.

  PMID: 23070637 BACKGROUND

• Phillips TJ, McGuirk SP, Chahal HK, Kingston J, Robertson F, Brew S, Roebuck D, Hungerford JL, Herod J. Autonomic cardio-respiratory reflex reactions and superselective ophthalmic arterial chemotherapy for retinoblastoma. Paediatr Anaesth. 2013 Oct;23(10):940-5. doi: 10.1111/pan.12162. Epub 2013 May 13.

  PMID: 23668238 BACKGROUND

• Kato MA, Green N, O'Connell K, Till SD, Kramer DJ, Al-Khelaifi M, Han JH, Pryor KO, Gobin YP, Proekt A. A retrospective analysis of severe intraoperative respiratory compliance changes during ophthalmic arterial chemosurgery for retinoblastoma. Paediatr Anaesth. 2015 Jun;25(6):595-602. doi: 10.1111/pan.12603. Epub 2015 Jan 7.

  PMID: 25565164 BACKGROUND

• Scharoun JH, Han JH, Gobin YP. Anesthesia for Ophthalmic Artery Chemosurgery. Anesthesiology. 2017 Jan;126(1):165-172. doi: 10.1097/ALN.0000000000001381. No abstract available.

  PMID: 27748655 BACKGROUND

MeSH Terms

Conditions

Retinoblastoma

Interventions

Nitroglycerin; Saline Solution

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Retinal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases

Intervention Hierarchy (Ancestors)

Nitro Compounds; Organic Chemicals; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Young-Eun Jang, MD

CONTACT

82-2-2072-3664; na0ag2@hotmail.com

Jin-Tae Kim, MD, PhD

CONTACT

82-2-2072-3664; jintae73@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Prior to the procedure, each patient will be randomized into either the saline-first arm or nitroglycerin-first arm. At the first intra-arterial chemotherapy after enrollment, saline or nitroglycerin is used according to the group allocation. At the second intra-arterial chemotherapy after enrollment, nitroglycerin is used for the saline-first arm, and saline is used for the nitroglycerin-first arm.

Study Record Dates

• First Submitted: September 2, 2020
• First Posted: September 25, 2020
• Study Start: September 28, 2020
• Primary Completion: June 30, 2024
• Study Completion: December 30, 2024
• Last Updated: November 22, 2023

Record last verified: 2023-11

Locations

KR (1)