Clinical trial NCT02832115: Topical Nitroglycerine Treatment for Radial Artery Spasm Prevention
Official title: Topical Nitroglycerine Treatment for Radial Artery Spasm Prevention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Radial Artery Spasm
Angina
Coronary Artery Disease
Keywords: Cardiac Catheterization
Vascular Access Site Complications
Vasodilator
Nitroglycerine
Lidocaine
Lead sponsor: Aultman Health Foundation
Sponsor class: OTHER
First posted: 2016-07-14
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary objective of the study is to determine the role of transdermal vasodilators as an adjunct to parenteral vasodilators in reducing radial artery spasm, improving patient comfort, and post procedure radial artery patency during transradial coronary angiograms and interventions. The study hypothesis is that transdermal vasodilators will increase radial artery size and reduce radial artery spasm as well as improve patient comfort and post procedure radial artery patency. This is a single-center, double-blind, randomized, placebo-controlled study comparing the effect of transdermal preparations of lidocaine + nitroglycerine and lidocaine + placebo on radial artery spasm in patients undergoing transdermal coronary angiograms. Prior to the procedure, each patient will be randomized into either the control arm, lidocaine + placebo, or study arm, lidocaine + nitroglycerine.

Detailed description: Background:

Vascular access site complications (VASC) during cardiac catheterizations are significantly higher in femoral access compared to radial access. Main disadvantage in radial access is the restriction in size of catheters as well as incidence of radial artery spasm. Radial spasm is identified by pain in the forearm aggravated by movement of the catheter/sheath; difficulty in manipulating the catheter; loss of radial pulse or damping of radial arterial pressure. Tortuosity and loops in upper extremity arterial tree could mimic some findings of radial artery spasm. Incidence of radial spasm has been reported to range between 4% and 20%. Risk factors include smaller radial artery diameter, atherosclerotic lesions, entrance of guidewires into side branches, vessel tortuosity, larger arterial sheath diameters, procedure duration, female sex, younger age, lower BMI, Diabetes, number of catheters used, volume of contrast, unsuccessful access at first attempt, fear and anxiety. Mean size of radial artery is reported at 2.44 mm. Women and persons of south Asian descent tend to have smaller radial arteries with means of 1.91mm and 2.00 mm respectively. Outer diameters of commonly used 5 French (5F) and 6 French (6F) sheaths are 2.16 mm and 2.62 mm respectively. Ratio of radial artery to sheath size affects post-procedural radial artery flow.

Transdermal vasodilators prior to vascular access would increase chance for successful arterial access in first attempt and increase radial artery to sheath size ratio both of which should have additive benefit to intraarterial (IA) vasodilators in reducing spasm. Transdermal lidocaine would reduce pain during subcutaneous lidocaine, which can further ameliorate the risk of radial artery spasm. Use of transdermal nitroglycerine has been shown to safely increase radial artery size without significant hypotension.

Aim:

To study the role of transdermal vasodilators as an adjunct to parenteral vasodilators, in reducing radial artery spasm and improving patient comfort and post procedure radial artery patency during radial coronary angiograms and interventions.

Hypothesis:

Transdermal vasodilators will increase radial artery size and reduce radial artery spasm as well as improve patient comfort and post procedure radial artery patency.

Study Design:

Single center, double blinded, randomized placebo-controlled study comparing effect of transdermal preparations of lidocaine + Nitroglycerine and lidocaine + placebo on radial artery spasm and procedural success in patients undergoing radial coronary angiograms and interventions. All patients will receive standard parenteral cocktail including intraarterial or intravenous (IV) heparin and IA nitroglycerine and / or verapamil. Exact doses and combinations would be at the discretion of individual provider based on patient's hemodynamic status and comorbid conditions.

End Points:

Primary:

1. Radial artery spasm: Incidence of radial artery spasm indicated by a Radial artery spasm score of 1 or more. Radial artery spasm score is sum of:

a. Verbal or nonverbal expression of discomfort in the forearm during catheter/sheath manipulation - Absent :0; Present:1 b. Difficulty in manipulating the catheter- Absence :0; Present:1 c. Difficulty with sheath removal: Absent: 0; Present:1 d. Additional use of IA nitroglycerine or verapamil after the initial vasodilator cocktail for suspected radial artery spasm- No:0; Yes:1.

Secondary:

1. Change in ipsilateral radial artery dimension (mm) before application of topical nitroglycerine / placebo (pre-dilation) vs. prior to arterial puncture after application of topical nitroglycerine / placebo (Post-dilation).
2. Procedural failure: Need to abort procedure or convert to femoral approach.
3. Patient forearm discomfort or pain during procedure measured using Visual analog scale 0-10.
4. Ipsilateral radial pulse at end of procedure 0-4+.

Safety endpoints:

1. Asymptomatic Hypotension: Systolic blood pressure (SBP) \< 90 mm Hg
2. Symptomatic Hypotension: Dizziness or lightheadedness and SBP \< 100 mm Hg
3. Intractable headache unrelieved by 1gm of acetaminophen

Adverse Effects of investigational product:

1. Hypotension: SBP \< 90 mm Hg requiring intervention any time after application of investigational product (IP) in Ambulatory Cardiac Unit (Same Day) until removal of IP in cathlab
2. Dizziness or lightheadedness requiring intervention any time after application of IP in Ambulatory Cardiac Unit (Same Day) until removal of IP in cathlab
3. Headache requiring intervention anytime after application of IP in Ambulatory Cardiac Unit (Same Day) until removal of IP in cathlab

Complications of Radial artery catheterization:

1. Forearm hematoma \> 5cm 2. Absent ipsilateral radial pulse (0) after procedure

Methods:

1. Patient enrollment:

   a. Outpatient: i. Whenever feasible, information about the study would be provided to the patient prior to arrival in Ambulatory Cardiac Unit (Same Day) (preferably at the time of scheduling). When not feasible, patients will be contacted via phone prior to the day of procedure or approached in the Ambulatory Cardiac Unit (Same Day) unit on the day of the procedure by one of the investigators to assess interest in participation.

   ii. Patients who are interested and meet all inclusion criteria and none of the exclusion criteria will be enrolled in the trial in the Ambulatory Cardiac Unit (Same Day) on the day of their scheduled procedure. One of the participating investigators will obtain informed consent after the patient has had time to review the consent and all questions have been answered.

   b. Inpatient: i. Hospitalized patients who are interested and meet all inclusion criteria and none of the exclusion criteria may be enrolled in the trial on or before the day of their scheduled procedure, but always prior to transfer to the Catheterization Lab. One of the participating investigators will obtain informed consent after the patient has had time to review the consent and all questions have been answered.
2. After reviewing the most current vital signs, patients without any exclusion criteria will be randomized 1:1 to control arm (40 mg Lidocaine + placebo) or study arm (40 mg lidocaine + 30 mg nitroglycerine)
3. Study drug assignment will be randomized and distributed by a delegated member of the study staff, with oversight by the PI or Sub-Is, for patients consented and enrolled in the trial at least 60 minutes prior to the procedure start time.
4. Pre-medication cross sectional image of ipsilateral radial artery (approximately 1 inch proximal to radial styloid process) will be recorded using bedside sonogram with no more than gentle pressure and site marked with a skin marker.
5. Ipsilateral wrist circumference (1 inch proximal to radial styloid process) will be documented.
6. Pre-procedure ipsilateral radial pulse strength (0-4+) will be documented. (4+ Bounding, 3+ Increased, 2+ Normal, 1+ Weak, 0+ Absent or nonpalpable)
7. Transdermal preparation will be applied to ipsilateral wrist overlying radial pulse (centered approximately 1 inch proximal to radial styloid process) at least 60 minutes before procedure start time at a dose of 40mg (6 ribbons of 2 inches each) of 5% Lidocaine and 30mg (8 ribbons of 2 inches each) of 2% Nitroglycerine/Placebo.
8. Patients will complete the Amsterdam Preoperative Anxiety and Information Scale (APAIS).
9. Vitals signs to be checked every 30 minutes (±10 minutes) after application of the topical preparation for 60 minutes (±10 minutes) then every 60 minutes (±10 minutes) until procedure.
10. If SBP \< 100 mm Hg and patient complains of dizziness or light-headedness or if SBP \< 90 mm Hg, the topical preparation will be removed promptly, 250 ml of 0.9% Normal Saline (NS) IV bolus will be given over 15 minutes, and provider will be notified immediately.
11. If patient complains of headache, one or two tablets of 500 mg acetaminophen will be given by mouth every 4 hours as needed. One tablet will be given if the patient reports a value of 0-3 on the pain scale, and two tablets will be given if the patient reports a value of 4 or greater on the pain scale. The maximum dose of acetaminophen is 4g in 24 hours.
12. If 30 minutes after acetaminophen administration, headache intensity ≥ 5/10 or patient unable to tolerate intensity of headache, the topical preparation will be removed promptly and provider will be notified immediately.
13. If any of the safety endpoints occur, an investigator will be notified immediately and further decision to proceed with cardiac catheterization or additional workup or treatment would be at the discretion of the investigator.
14. Immediately prior to sterile preparation of access site, transdermal preparation will be removed in Cath Lab and post-dilation cross sectional image of ipsilateral radial artery (approximately 1 inch proximal to radial styloid process) will be captured using bedside sonogram applying no more than gentle pressure.
15. Conscious sedation with IV fentanyl and midazolam given with exact dosing at operator's discretion (based on patient's hemodynamic status and comorbid conditions).
16. After sterile preparation 0.5 - 1.0 ml of subcutaneous lidocaine is administered and radial artery cannulated using modified seldinger technique with 5F or 6F hydrophilic sheath.
17. Parenteral radial cocktail (IV/IA heparin +/- IA nitroglycerine +/- IA verapamil) is given with exact combination and dose at discretion of operator based on patient's hemodynamic status.
18. Coronary angiogram and or intervention performed adopting best practices with care to minimize procedure time, contrast volume and catheter exchanges and avoiding side branches.
19. Following parameters are documented:

    1. Patient demographics (Age, Sex, BMI, Race)
    2. Conscious sedation drugs and doses used
    3. Sheath size
    4. Number of arterial sticks before arterial access: One or more (Blood in arteriotomy needle equates arterial stick)
    5. Wire passage in one or more attempts
    6. Sheath insertion in one or more attempts
    7. Radial parenteral cocktail used
    8. Radial artery spasm score:
    9. Verbal or nonverbal expression of discomfort in the forearm during catheter/sheath manipulation - Absent:0; Present:1 ii. Difficulty in manipulating the catheter - Absent:0; Present:1 iii. Difficulty in sheath removal - Absent:0; Present:1 iv. Additional use of IA nitroglycerine or verapamil after the initial vasodilator cocktail for suspected radial artery spasm - No:0; Yes:1

    i. Use of long sheath j. Use of hydrophilic wires or catheters k. Tortuosity of upper extremity vessels / anatomic variants l. Catheters used m. Contrast volume n. Difficulty in removing catheters and sheath o. Use of IA/IV nitroglycerine and/or verapamil at end of procedure for sheath removal: provisional use when radial artery spasm present or suspected vs. routine pre-emptive use to avoid radial artery spasm per operator standard practice.

    p. Length of procedure q. Change to femoral arterial access and reason r. Procedures performed
20. Patient's perceived peri-procedure forearm discomfort documented using VAS (1-10) at the completion of the procedure
21. Post procedure strength of ipsilateral radial pulse (0-4+) after radial band removal documented and presence and size of hematoma at access site at time of radial band removal documented
22. For patients who have the sheath left in place for percutaneous coronary intervention (PCI) as a separate procedure at a later time, data will be collected for the initial diagnostic catheterization only. The procedure will be considered completed with removal of last diagnostic catheter. Post procedure pulse will be the radial pulse after the PCI.
23. Patients are monitored for adverse events for the following duration:

    a. For patients discharged home from the ambulatory cardiac unit (same day unit) after procedure completion: i. Until discharged home b. For hospitalized patients: i. Until 120 minutes after Radial band, or comparable product, removal

Eligibility criteria: Inclusion Criteria:

1. Age: 18 years or older
2. Radial artery catheterization

Exclusion Criteria:

1. Hypersensitivity or contraindication to lidocaine
2. Hypersensitivity or contraindication to nitroglycerine
3. Recent use of phosphodiesterase 5 inhibitors (\<24 hours after sildenafil or vardenafil; \<48 hours after tadalafil)
4. Baseline weak radial pulse (0 or 1+)
5. Baseline hypotension SBP \< 100 mmHg at the time of enrollment
6. Dizziness or light-headedness at the time of enrollment
7. Severe Aortic Stenosis or Hypertrophic obstructive cardiomyopathy
8. Previous unknown bypass grafts or known left internal mammary graft
9. Chest pain within 6 hours of IP administration
10. More than 2 episodes of chest pain within 24 hours prior to IP administration
11. Use of sublingual, transdermal, or intravenous nitroglycerine within 6 hours prior to IP administration
12. Likely need for use of nitroglycerine for non-study indication
13. Narcotic or sedative within 4 hours of enrollment
14. Women who are suspected or known to be pregnant or breastfeeding

Primary outcomes:
measure: Radial Artery Spasm
timeFrame: Intraprocedural: From procedure start to application of radial band. Approximate time 30 to 90 minutes.
Secondary outcomes:
measure: Change in Radial Artery Dimension Measured in mm^2.
timeFrame: Application of nitroglycerine / placebo until prior to arterial puncture. Approximate 60 to 120 minutes
measure: Number of Patients With Procedural Failure
timeFrame: Intraprocedural: From procedure start to application of radial band. Approximate time 30 to 90 minutes.
measure: Patient Discomfort or Pain During Procedure (Visual Analog Scale 0-10)
timeFrame: Intraprocedural: From procedure start to application of radial band. Approximate time 30 to 90 minutes.
measure: Radial Pulse at End of Procedure
timeFrame: At the end of transradial cardiac catheterization after sheath removal
Other outcomes:
Locations:
city: Canton
country: United States
facility: Aultman Hospital
state: Ohio
Study officials:
affiliation: Aultman Hospital
name: Prabhakaran Gopalakrishnan, MD
role: PRINCIPAL_INVESTIGATOR
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