Clinical trial NCT04564521: Nitroglycerin for Intra-arterial Chemotherapy in Pediatric Retinoblastoma.
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Retinoblastoma
Keywords: Intra-arterial chemotherapy
Cardio-respiratory side effects
Nitroglycerin
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2020-09-25
Enrollment: 36
Sex: ALL
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: The incidence of the cardio-respiratory side effects during ophthalmic artery selection and intra-arterial injection of chemotherapy agents. (percent)
timeFrame: During the intra-arterial chemotherapy (up to 4 hour)
Secondary outcomes:
measure: The duration of the cardio-respiratory side effects during ophthalmic artery selection and intra-arterial injection of chemotherapy agents. (percent)
timeFrame: During and after the intra-arterial chemotherapy (up to 48 hour)
measure: The incidence of using vaso-active drugs (percent)
timeFrame: During and after the intra-arterial chemotherapy (up to 48 hour)
measure: The incidence of the side effect of nitroglycerin infusion (percent)
timeFrame: During the intra-arterial chemotherapy (up to 4 hour)
measure: The concentration of inhaled sevoflurane (vol%)
timeFrame: During the intra-arterial chemotherapy (up to 4 hour)
measure: The depth of anesthesia
timeFrame: During the intra-arterial chemotherapy (up to 4 hour)
measure: Duration of anesthesia (min)
timeFrame: During the intra-arterial chemotherapy (up to 4 hour)
measure: Total procedure time (min)
timeFrame: During the intra-arterial chemotherapy (up to 4 hour)
measure: The procedural satisfaction score of radiologist (1-3)
timeFrame: During the intra-arterial chemotherapy (up to 4 hour)
measure: Incidence of the newly developed focal ischemia or infarct in retina photography(yes or no)
timeFrame: After the intra-arterial chemotherapy (up to 6 month)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Jin-Tae Kim
Study officials:
References:
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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.
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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.
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.
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.