Topical Nitroglycerine Treatment for Radial Artery Spasm Prevention
Phase: PHASE4
Conditions: Radial Artery Spasm, Angina, Coronary Artery Disease
Sponsor: Aultman Health Foundation

Topical Nitroglycerine Treatment for Radial Artery Spasm Prevention 
(TNT-RASP) 
 
NCT02832115  
 
October 4 2020 
 

Background: 
Vascular access site complications (VASC) during cardiac catheterizations are significantly higher 
in transfemoral access compared to transradial 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, DM, 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 5F and 6F sheaths are 
2.16 mm and 2.62 mm, respectively. Ratio of radial artery to sheath size affects post-procedural 
radial artery flow.  
Intraarterial vasodilators reduce radial artery spasm. 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 
vasodilators in reducing spasm. Transdermal lidocaine would reduce pain during s.c. 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 transradial 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 transradial coronary angiograms and 
interventions. All patients will receive standard parenteral cocktail including intraarterial or 
intravenous heparin and intraarterial 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 intraarterial nitroglycerine or verapamil after the initial 
vasodilator cocktail for suspected radial artery spasm- No:0; Yes:1. 
Secondary: 
1. Change in ipsilateral radial artery cross sectional area (mm^2) before application of 
topical nitroglycerine / placebo (pre-dilation) vs. prior to arterial puncture after 
application of topical nitroglycerine / placebo (Post-dilation). 
2. Number of patients with Procedural failure: Need to abort procedure or convert to 
transfemoral approach. 
3. Patient forearm discomfort or pain during procedure measured using Visual analog 
scale 0-10, 0 being no discomfort or pain (best) and 10 being worst discomfort or pain 
(worst).  
4. Ipsilateral radial pulse at end of procedure 0-4+, 0 indicating no palpable pulse 
(worst); 1 + indicating a faint, but detectable pulse; 2 + suggesting a slightly more 
diminished pulse than normal; 3 + is a normal pulse; and 4 + indicating a bounding pulse 
(best). 
Safety endpoints: 
1. Asymptomatic Hypotension: 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 
Cath lab 

2. Dizziness or lightheadedness requiring intervention any time after application of IP in 
Ambulatory Cardiac Unit (Same Day) until removal of IP in Cath lab 
3. Headache requiring intervention any time after application of IP in Ambulatory 
Cardiac Unit (Same Day) until removal of IP in Cath lab 
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 intravenous 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: 
a. Patient demographics (Age, Sex, BMI, Race) 
b. Conscious sedation drugs and doses used 
c. Sheath size 
d. Number of arterial sticks before arterial access: One or more (Blood in arteriotomy 
needle equates arterial stick) 
e. Wire passage in one or more attempts 
f. Sheath insertion in one or more attempts 
g. Radial parenteral cocktail used 
h. Radial artery spasm score:  
i. 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 intraarterial 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 UE vessels / anatomic variants 
l. Catheters used 
m. Contrast volume 

n. Difficulty in removing catheters and sheath 
o. Use of IA/IV NTG 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 
Inclusion criteria: 
1. Age: 18 years or older 
2. Radial artery catheterization +/- intervention 
Exclusion criteria: 
1. Hypersensitivity or contraindication to lidocaine 
2. Hypersensitivity or contraindication to nitroglycerine 
3. Recent use of PDE5 inhibitors (<24 hours after sildenafil or vardenafil; <48 hours after 
tadalafil) 
4. Baseline weak radial pulse (0 or 1+) 

5. Baseline hypotension SBP < 100mmHg at the time of enrollment 
6. Dizziness or light-headedness at the time of enrollment 
7. Severe Aortic Stenosis or HOCM 
8. Previous unknown bypass grafts or known LIMA 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 
 
Processing of cross sectional sonographic images of radial artery: 
1. Horizontal diameter 
2. Vertical diameter 
3. Average diameter 
4. Cross Sectional area 
5. Presence of atherosclerotic plaque 
 
Data and Safety Monitoring Plan 
A data safety monitoring committee will be assigned to review each case for eligibility, 
adherence to the protocol, occurrence of adverse events, and accuracy of data. This will be 
completed on a regular basis. The first review will be conducted after enrolling the first 10 
patients. Regular reviews will be scheduled at increments of 50 randomized patients until 
enrollment goals are met. Any deficiencies found during this review will be addressed and 
reported to necessary parties. 
 
Statistical Analysis 
Outcomes will be analyzed by intention to treat analysis using SPSS software. Relationship 
between use of nitroglycerine and radial spasm will be analyzed using Pearson Chi Square test. 
The radial artery dimensions before and after application of the study drug or placebo will be 
compared using paired sample t test. Relationship between use of nitroglycerine and procedural 
failure will be analyzed using Pearson Chi Square test. Relationship between use of 
nitroglycerine and forearm discomfort or pain during procedure measured using Visual analog 

scale will be analyzed using Mann Whitney test. The post procedure pulse will be analyzed using 
Mann Whitney test.  
 
Privacy Protections 
It is not possible to conduct this research study without access to and the use of the patients’ 
medical record information. The researcher (s) will only obtain the minimum necessary data to 
achieve the goals of the research.  The data collected is not sensitive in nature.  In this research 
project access to and the use of participants PHI involves no more than minimal risk to the 
privacy of the individual because the investigator(s) is (are) directly involved in the care of 
respective subjects as part of their patient care responsibilities. Granting of a Partial Waiver of 
HIPAA authorization for recruitment purposes will not adversely affect the privacy of the 
involved patients or the confidentiality of their medical record information.       
 
Confidentiality Protections 
Identifiable health information will not be reused or disclosed to any other person or entity, except 
as required by law, for authorized oversight of the research study, or for other permitted research 
purposes. Research records will be secured in a locked file cabinet in an access-controlled 
office.  Electronic records will be maintained on an Aultman server using identification and secure 
password.  Records containing PHI will be limited in access to the research team only.   
Research records will be securely stored in accordance with retention requirements of local and 
national regulations.  The minimum obligations will be six (6) years following study closure.  The 
ICF states that patient records will be stored up to 10 years.  After this time records may be 
destroyed, the method of destruction will be by shredding per institutional policy.   
Information from the study may be published in study reports, scientific journals or presented at 
scientific meetings; however, the individual and group identity will be kept strictly 
confidential.  Only with specific permission can names or other identifiers used in any publication 
or teaching material.   
 
HIPAA Authorization 
The researcher will obtain an Authorization to Use and/or Disclose of Individually Identifiable 
Health Information for Research Purposes as part of the informed consent process (see attached 
consent document).  The following individuals/organizations may have access to research data but 
are required to make sure the information is kept private, unless required by law to provide 
information: 
• The Aultman Cardiology Research Group is sponsoring this study. The following 
individuals/organizations may inspect the research records. The Human Research Review 
Board, HRRB, is a group of people who review the research with the goal of protecting 
the people who take part in the study. 

• The research staff, including the Principal Investigator and Sub-Investigators listed on 
page one of this document, along with other members of the research team responsible 
for collecting and analyzing data.  
• The Food and Drug Administration 
 

Pre- Procedure anxiety evaluation: 
The Amsterdam Preoperative Anxiety and Information Scale (APAIS) 
Not at all 
1 2 3 4 5 Extremely 
1. I am worried about the sedation 
 
 
 
 
 
2. The sedation is on my mind 
continually 
 
 
 
 
 
3. I would like to know as much as 
possible about the sedation 
 
 
 
 
 
4. I am worried about the procedure 
 
 
 
 
 
5. The procedure is on my mind 
continually 
 
 
 
 
 
6. I would like to know as much as 
possible about the procedure 
 
 
 
 
 
Below information will be calculated later based on patient replies for above questions but 
will not be included in the patient form 
The subscales 
Sedation-related anxiety 
Sum A = 1 + 2 
Surgery-related anxiety 
Sum S = 4 + 5 
Information desire component 
= 3 + 6 
Combined anxiety component 
Sum C = sum A + sum S (1 + 2 + 4 + 5) 
 
 
 
 

Visual Analog Scale for peri-procedure pain: