Nitroglycerin for Intra-arterial Chemotherapy in Pediatric Retinoblastoma.

Retinoblastoma Clinical Trial

Official title:

The Effect of Nitroglycerin on the Incidence of Cardiorespiratory Side Effect During the Intra-arterial Chemotherapy in Pediatric Patients With Retinoblastoma: a Randomized, Double-blind, Placebo-controlled, Crossover Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04564521
• Other study ID #: 2006-108-1134
• Status: Recruiting
• Phase: N/A
• Start date: September 28, 2020
• Est. completion date: December 30, 2024

Study information

• Verified date: November 2023
• Source: Seoul National University Hospital
• Contact: Young-Eun Jang, MD
• Phone: 82-2-2072-3664
• Email: na0ag2[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: December 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 7 Years

Eligibility

Inclusion Criteria:

• Retinoblastoma patients who need intra-arterial chemotherapy under general anesthesia

• Residual intra-arterial chemotherapy = 2 times (cross-over design)

Exclusion Criteria:

• 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)

Related Conditions & MeSH terms

• Retinoblastoma

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Jin-Tae Kim	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The duration of the cardio-respiratory side effects during ophthalmic artery selection and intra-arterial injection of chemotherapy agents. (percent)	Duration between the onset and the recovery from cardio-respiratory side effects.	During and after the intra-arterial chemotherapy (up to 48 hour)
Secondary	The incidence of using vaso-active drugs (percent)	The incidence of using vaso-active drugs (e.g. vasopressor, inotropics)(percent)	During and after the intra-arterial chemotherapy (up to 48 hour)
Secondary	The incidence of the side effect of nitroglycerin infusion (percent)	Hypotension (< 80% of baseline) after 10 minutes from nitroglycerin infusion, or allergic reaction, etc.	During the intra-arterial chemotherapy (up to 4 hour)
Secondary	The concentration of inhaled sevoflurane (vol%)	The concentration of inhaled sevoflurane	During the intra-arterial chemotherapy (up to 4 hour)
Secondary	The depth of anesthesia	The depth of anesthesia (bispectral index or patient sedation index, 0-100, 0 smaller score means deep anesthesia and larger score means awake state.)	During the intra-arterial chemotherapy (up to 4 hour)
Secondary	Duration of anesthesia (min)	Duration of anesthesia	During the intra-arterial chemotherapy (up to 4 hour)
Secondary	Total procedure time (min)	From ophthalmic artery selection to the end of intra-arterial injection.	During the intra-arterial chemotherapy (up to 4 hour)
Secondary	The procedural satisfaction score of radiologist (1-3)	3 grades (1:poor, 2:fair, 3:good)	During the intra-arterial chemotherapy (up to 4 hour)
Secondary	Incidence of the newly developed focal ischemia or infarct in retina photography(yes or no)	Incidence of the newly developed focal ischemia or infarct in retina photography(yes or no) on ophthalmology outpatient clinic after the intra-arterial chemotherapy assessed by pediatric ophthalmologist	After the intra-arterial chemotherapy (up to 6 month)