Hemodynamic InstabilityEarly Phase 1TOPIACNCT02955524
Topical Anesthesia and Intra-arterial Chemotherapy for Retinoblastoma
A Early Phase 1 study testing Tetracaine 0.5% and Lidocaine hydrochloride ophthalmic gel 3.5% in people with Hemodynamic Instability, run by University of Miami.
Trial summary
The objective of this study is to use local topical anesthesia to numb the sensory input, captured by branches of the Trigeminal nerve found on the skin in and around the eye, to decrease a hemodynamic reflex seen during placement of a catheter for intra-arterial chemotherapy (IAC) for eye tumors in children. Read more about this study
- Who is it for?
- Ages 8 weeks and older
- Conditions the study is for
- Hemodynamic Instability
- What is being tested?
- Tetracaine 0.5% and Lidocaine hydrochloride ophthalmic gel 3.5%
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Mar 2018to Dec 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 weeks and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Children with Retinoblastoma diagnosis scheduled for Intra-arterial chemotherapy under general anesthesia
Who cannot join
- any candidate with history of allergy to anesthetics or preservatives used in local anesthetics any candidate that has a history of allergic dermatitis any candidate that has an open wound in and around the eye to be treated
About this study
Official title: Topical Anesthesia to Decrease the Trigeminal-Cardiac Reflex During Intra-arterial Injection of Chemotherapy for Retinoblastoma in Children.
The objective of this study is to use local topical anesthesia to numb the sensory input, captured by branches of the Trigeminal nerve found on the skin in and around the eye, to decrease a hemodynamic reflex seen during placement of a catheter for intra-arterial chemotherapy (IAC) for eye tumors in children. This Trigeminal-cardiac reflex brings about hemodynamic instability during general anesthesia.
Normally, one could block this sensorial input with ophthalmic peribulbar placement of local anesthetics, but these eyes have malignant growth and invasive procedures may cause more harm. The investigators are aiming to numb the sensory branches of the trigeminal nerve non-invasively and observe for any decrease in these events.
Read the detailed description
Retinoblastoma is a rare tumor of the eye and accounts for 6% of malignancies in children less than 5 years of age. Pediatric anesthesiologists have observed a series of hemodynamic instability following the insertion of a catheter into the cavernous segment of the internal carotid artery or during manipulation of a micro-catheter into the ophthalmic artery for intra-arterial chemotherapy (IAC) of retinoblastoma cases by neuroradiologists. This reaction has been recently published in case reports and observational studies as the treatment of these tumors have moved into the interventional imaging suites. This reaction closely resembles the "diving reflex" seen when a person is submerged in cold water; known as the trigeminal-cardiac reflex. It manifests as a sudden hemodynamic disturbance in arterial blood pressure, heart rate, arrhythmia and changes in pulmonary compliance.Rescue from a trigeminal-cardiac reflex entails increasing intravascular volume, administrating mild to resuscitative doses of epinephrine and ventilatory support.
Catheter manipulation around the ophthalmic artery can stimulate the afferent pathway of the trigeminal nerve, branches V1 and V2, originating around the eye to be treated.The ethmoidal nerve, from the nasal passage on the same side, is also stimulated. This in turn triggers a response by the vagus nerve with hemodynamic instability.
Method: Participants are placed under general endotracheal anesthesia for this scheduled procedure. One drop of ocular antiseptic (betadine 5%) will be placed in the eye to be treated followed by a drop of topical FDA approved local anesthetic, Tetracaine 0.5%, to the nasolacrimal duct ( inner corner of the eye) on the eye to be treated. This will numb the ethmoidal nerve in the nasal passage. This is followed by 1 ml of 3.5% Lidocaine gel to the surface of the eye. This gel is placed on the surface of the eye and skin around the eye to numb V1 and V2 fibers of the trigeminal nerve. The study will observe if there is any decrease in the intensity of the reflex or incidence of the reflex during placement of the micro-catheter.
- Conditions
- Hemodynamic Instability
- Being tested
- Tetracaine 0.5%, Lidocaine hydrochloride ophthalmic gel 3.5%
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tetracaine 0.5%Drug
One drop of 0.5% Proparacaine to nasolacrimal Duct to numb the ethmoidal nerve in the nasal passage on the side of the eye to be treated.
Lidocaine hydrochloride ophthalmic gel 3.5%Drug
Also called Akten
1ml of lidocaine gel is placed over the conjunctivae of the eye to be treated after the patient is under general anesthesia and before the procedure
| Study group | Role | What they receive |
|---|---|---|
| Treatment session 1a | Experimental | Topical ophthalmic anesthesia to participants (#) on each session (letter) of intra-arterial chemotherapy.
where #1 is the participant identifier and letter-a is the start session with study protocol (most candidates will receive more than 4 sessions in a 6 month period) Receives: Drug: Tetracaine 0.5%; Drug: Lidocaine hydrochloride ophthalmic gel 3.5% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decrease in systolic Blood Pressure
Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.
Measured: 5 seconds
Drop in end-tidal C02
Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.
Measured: 5 seconds
Decrease in lung compliance
Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.
Measured: 5 seconds
Decrease in oxygen saturation
Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.
Measured: 5 seconds
Cardiac arrythmia
Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.
Measured: 5 seconds
Secondary outcomes (1)
Recovery from Trigeminal-cardiac event
Investigator will communicate when the event is over or rescue drugs given.
Measured: 2 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2016 (estimated)
- Study startMar 2018 (estimated)
- Primary completionJun 2020 (estimated)
- Study completionDec 2020 (estimated)
Why it stopped: I discontinued this study because I transferred to another institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hemodynamic InstabilityStudies of the same condition, open and under way.
- More trials run by University of MiamiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Miami
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jacqueline L Tutiven, University of Miami
- Investigators
- Jacqueline Tutiven, MD, Principal investigator, Director Pediatric Anesthesia Fellowship/Assistant ProfessorNorman Halliday, MD, Study chair, Chief, Pediatric Anesthesiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02955524
- Sponsor's protocol ID
- 20161001
- Acronym
- TOPIAC
- Status last verified
- Apr 2018
- First submitted
- 2 Nov 2016
- Last updated
- 20 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27748655Jabbour P, Chalouhi N, Tjoumakaris S, Gonzalez LF, Dumont AS, Chitale R, Rosenwasser R, Bianciotto CG, Shields C. Pearls and pitfalls of intraarterial chemotherapy for retinoblastoma. J Neurosurg Pediatr. 2012 Sep;10(3):175-81. doi: 10.3171/2012.5.PEDS1277. Epub 2012 Jul 13.
PubMed 22793160
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Topical Anesthesia to Decrease the Trigeminal-Cardiac Reflex During Intra-arterial Injection of Chemotherapy for Retinoblastoma in Children.
- ClinicalTrials.gov ID
- NCT02955524
- Acronym / sponsor ID
- TOPIAC / 20161001
- Conditions
- Hemodynamic Instability
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: I discontinued this study because I transferred to another institution.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of MiamiUniversity, hospital or other
- Study start
- Mar 2018 (estimated)
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 4 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to use local topical anesthesia to numb the sensory input, captured by branches of the Trigeminal nerve found on the skin in and around the eye, to decrease a hemodynamic reflex seen during placement of a catheter for intra-arterial chemotherapy (IAC) for eye tumors in children. This Trigeminal-cardiac reflex brings about hemodynamic instability during general anesthesia.
Normally, one could block this sensorial input with ophthalmic peribulbar placement of local anesthetics, but these eyes have malignant growth and invasive procedures may cause more harm. The investigators are aiming to numb the sensory branches of the trigeminal nerve non-invasively and observe for any decrease in these events.
Detailed description
Retinoblastoma is a rare tumor of the eye and accounts for 6% of malignancies in children less than 5 years of age. Pediatric anesthesiologists have observed a series of hemodynamic instability following the insertion of a catheter into the cavernous segment of the internal carotid artery or during manipulation of a micro-catheter into the ophthalmic artery for intra-arterial chemotherapy (IAC) of retinoblastoma cases by neuroradiologists. This reaction has been recently published in case reports and observational studies as the treatment of these tumors have moved into the interventional imaging suites. This reaction closely resembles the "diving reflex" seen when a person is submerged in cold water; known as the trigeminal-cardiac reflex. It manifests as a sudden hemodynamic disturbance in arterial blood pressure, heart rate, arrhythmia and changes in pulmonary compliance.Rescue from a trigeminal-cardiac reflex entails increasing intravascular volume, administrating mild to resuscitative doses of epinephrine and ventilatory support.
Catheter manipulation around the ophthalmic artery can stimulate the afferent pathway of the trigeminal nerve, branches V1 and V2, originating around the eye to be treated.The ethmoidal nerve, from the nasal passage on the same side, is also stimulated. This in turn triggers a response by the vagus nerve with hemodynamic instability.
Method: Participants are placed under general endotracheal anesthesia for this scheduled procedure. One drop of ocular antiseptic (betadine 5%) will be placed in the eye to be treated followed by a drop of topical FDA approved local anesthetic, Tetracaine 0.5%, to the nasolacrimal duct ( inner corner of the eye) on the eye to be treated. This will numb the ethmoidal nerve in the nasal passage. This is followed by 1 ml of 3.5% Lidocaine gel to the surface of the eye. This gel is placed on the surface of the eye and skin around the eye to numb V1 and V2 fibers of the trigeminal nerve. The study will observe if there is any decrease in the intensity of the reflex or incidence of the reflex during placement of the micro-catheter.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment session 1a | Experimental | Drug: Tetracaine 0.5%, Drug: Lidocaine hydrochloride ophthalmic gel 3.5%Topical ophthalmic anesthesia to participants (#) on each session (letter) of intra-arterial chemotherapy. where #1 is the participant identifier and letter-a is the start session with study protocol (most candidates will receive more than 4 sessions in a 6 month period) |
Who may qualify
- Ages
- 8 weeks and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Children with Retinoblastoma diagnosis scheduled for Intra-arterial chemotherapy under general anesthesia
Key exclusion criteria (1 listed)
- any candidate with history of allergy to anesthetics or preservatives used in local anesthetics any candidate that has a history of allergic dermatitis any candidate that has an open wound in and around the eye to be treated
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tetracaine 0.5%One drop of 0.5% Proparacaine to nasolacrimal Duct to numb the ethmoidal nerve in the nasal passage on the side of the eye to be treated. | Drug | Treatment session 1a |
| Lidocaine hydrochloride ophthalmic gel 3.5%Also: Akten1ml of lidocaine gel is placed over the conjunctivae of the eye to be treated after the patient is under general anesthesia and before the procedure | Drug | Treatment session 1a |
Primary outcome
Decrease in systolic Blood Pressure
Time frame: 5 seconds
Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.
Drop in end-tidal C02
Time frame: 5 seconds
Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.
Decrease in lung compliance
Time frame: 5 seconds
Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.
Decrease in oxygen saturation
Time frame: 5 seconds
Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.
Cardiac arrythmia
Time frame: 5 seconds
Interventionalist will communicate to the investigator of the catheter placement and our outcome measure will be recorded soon after.
1 secondary outcome
Recovery from Trigeminal-cardiac event
Time frame: 2 minutes
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2018.
- Results publication: PubMed 27748655Scharoun 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.
- Results publication: PubMed 22793160Jabbour P, Chalouhi N, Tjoumakaris S, Gonzalez LF, Dumont AS, Chitale R, Rosenwasser R, Bianciotto CG, Shields C. Pearls and pitfalls of intraarterial chemotherapy for retinoblastoma. J Neurosurg Pediatr. 2012 Sep;10(3):175-81. doi: 10.3171/2012.5.PEDS1277. Epub 2012 Jul 13.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacqueline Tutiven, MD principal investigator
Director Pediatric Anesthesia Fellowship/Assistant Professor
Norman Halliday, MD study chair
Chief, Pediatric Anesthesiology
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Tetracaine 0.5% and Lidocaine hydrochloride ophthalmic gel 3.5% in people with Hemodynamic Instability, run by University of Miami.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 20 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Decrease in systolic Blood Pressure (time frame: 5 seconds). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02955524, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2018.