Nitroglycerin for Intra-arterial Chemotherapy in Pediatric Retinoblastoma.

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Retinoblastoma

Intervention / Treatment
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* Drug: Nitroglycerin
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Maximum Age: 7 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nitroglycerin<br>Intravenous nitroglycerin (0.5mcg/kg/min) is infused after the induction of general anesthesia and during intra-arterial chemotherapy. | Drug: Nitroglycerin<br>* 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.<br>* Other names: Intravenous nitroglycerin;|
| Active Comparator: Normal saline<br>Normal saline is infused after the induction of general anesthesia and during intra-arterial chemotherapy. | Drug: Normal saline<br>* Intravenous normal saline is infused after the induction of general anesthesia and during intra-arterial chemotherapy as an active comparator.<br>* Other names: Intravenous normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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) | 
| The concentration of inhaled sevoflurane (vol%) | The concentration of inhaled sevoflurane | During the intra-arterial chemotherapy (up to 4 hour) | 
| 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) | 
| Duration of anesthesia (min) | Duration of anesthesia | During the intra-arterial chemotherapy (up to 4 hour) | 
| Total procedure time (min) | From ophthalmic artery selection to the end of intra-arterial injection. | During the intra-arterial chemotherapy (up to 4 hour) | 
| 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intra-arterial chemotherapy, Cardio-respiratory side effects, Nitroglycerin