Clinical trial NCT02832115
Conditions: Radial Artery Spasm Angina Coronary Artery Disease
Keywords: Cardiac Catheterization Vascular Access Site Complications Vasodilator Nitroglycerine Lidocaine
Sponsor: Aultman Health Foundation
Start date: 2016-09-01; Completion date: 2019-05-02
Enrollment: 100 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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

Arms: arm 1: 40 mg of topical lidocaine and 30 mg of topical nitroglycerine is applied to the wrist overlying radial pulse (centered approximately 1 inch proximal to the radial styloid process) at least 60 minutes before arterial puncture. Immediately prior to sterile preparation of access site, transdermal preparation will be removed in the cath lab. arm 2: 40 mg of topical lidocaine and placebo is applied to the wrist overlying radial pulse (centered approximately 1 inch proximal to the radial styloid process) at least 60 minutes before arterial puncture. Immediately prior to sterile preparation of access site, transdermal preparation will be removed in the cath lab.
Interventions: intervention 1: Topical Nitroglycerine intervention 2: Topical Lidocaine
Intervention descriptions: intervention 1: Topical nitroglycerine is applied to wrist prior to transradial cardiac catheterization to dilate radial artery and reduce spasm in study arm patients intervention 2: Topical Lidocaine is applied to wrist prior to transradial cardiac catheterization in both study and control arms

Protocol documents:
Prot_SAP_001.pdf: 
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: 
 

ICF_000.pdf: 
 
TNT-RASP Protocol [Version 3, Amendment 2; 14-Jul-2016] 
Consent Document Version: 3.0; 14-Jul-2016 
Approved by HRRB:   07-Sep-2016 
Page 1 of 17 
Topical Nitroglycerine Treatment for Radial Artery Spasm Prevention 
(TNT-RASP) 
 
NCT02832115  
 
September 19 2017 
 
 


 
TNT-RASP Protocol [Version 3, Amendment 2; 14-Jul-2016] 
Consent Document Version: 3.0; 14-Jul-2016 
Approved by HRRB:   07-Sep-2016 
Page 2 of 17 
INFORMED CONSENT DOCUMENT FOR PARTICIPATION 
OF A SUBJECT IN A RESEARCH STUDY 
 
Transdermal Nitroglycerine Treatment for Radial Artery 
Spasm Prevention 
TNT-RASP 
Principal Investigator 
Prabhakaran Gopalakrishnan, MD 
Sub-Investigators 
Sandeep Anreddy, MD 
Brendan K. Duffy, MD 
Nagapradeep Nagajothi, MD 
John J. Paulowski, MD 
Ramana Podugu, MD 
Rizwan Sardar, MD 
Sourabh Prabhakar, MD 
 
Aultman Cardiology Clinical Trials 
2600 Sixth Street, South West 
Canton, OH 44710 
Phone Number: (330) 363-7274 
24 Hour Phone Number: (330) 454-8076 
Aultman Hospital 
2600 Sixth Street, South West 
Canton, OH 44710 
 
 
INTRODUCTION 
You are being asked to participate in a clinical trial, a type of research study.  This consent 
document provides you with important information about the trial to decide if you want to 
participate.  It will outline the purpose of the study, the procedures involved, any possible risks 
associated with participation, and your rights as a participant. 
Please take time to completely and carefully read the consent document.  You will be able to ask 
the study doctor and study staff any questions you may have.  You may also discuss your 
participation in the trial with your primary physician and family. 
If you agree to participate in this study, you will be asked to sign this consent form.  You will 
then receive a copy of the signed document. 
In order to participate in this study you will be required to sign both this consent document and 
the authorization document. 


 
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Your participation in this study is voluntary.  You are free to say yes or no.  If you choose not to 
participate, your regular medical care and legal rights will not be affected.  If you decide to 
participate, you are permitted to withdraw your consent and stop at any time. 
This is a clinical trial, a type of research study.  Your study doctor will explain the clinical trial 
to you.  Clinical trials include only people who choose to take part.  Please take your time to 
make your decision about taking part.  You may discuss your decision with your friends and 
family.  You can also discuss it with your health care team.  If you have any questions, you can 
ask your study doctor for more explanation. 
WHO IS CONDUCTING THIS STUDY? 
Dr. Prabhakaran Gopalakrishnan, a Cardiology Fellow at Aultman Hospital, and Dr. 
Nagapradeep Nagajothi, an Interventional cardiologist and Program director of the Cardiology 
Fellowship at Aultman Hospital, are responsible for conducting this clinical study. Dr. Brendan 
Duffy, an interventional cardiologist is responsible for the study design and compliance with 
regulations.    
DO I HAVE TO BE IN THIS STUDY? 
You can decide whether to take part in this study or not.  You are free to say yes or no.  If you 
say no, your regular medical care will not change.  Even if you join this study, you do not have 
to stay in it.  You may stop at any time.   
A research study is different from routine medical care in three ways:  1) there are extra risks that 
we will tell you about in this form; 2) you may have some extra medical tests and visits; 3) the 
study procedures, tests and visits follow a set plan that must be kept. 
WHO CAN TAKE PART IN THIS STUDY? 
You are being asked to take part in this study because you are having a cardiac catheterization by 
transradial approach (using the artery in your wrist). 
WHAT IS THE USUAL APPROACH FOR CARDIAC 
CATHETERIZATION? 
Cardiac catheterization can be done either by transfemoral approach (i.e., using the artery in your 
thigh) or transradial approach (i.e., using the artery in your wrist). While each approach has its 
merits and limitations, your provider has elected for you to undergo a transradial approach. 
While transradial approach has been shown to have lower risk of complications as well as 
improved patient discomfort, the smaller size of the radial artery (artery in wrist) may lead to 
difficulties during the procedure in a small fraction of patients undergoing the procedure. You 
will be asked to lie flat on the operating table and medications will be given to help you relax. 
Your provider will administer a subcutaneous local anesthetic injection (to block pain sensation) 


 
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as well as vasodilatory medications directly into the artery (to improve its size), during the 
procedure. A sheath (small tube) will be inserted into the radial artery. Medications are given 
through the tube to help relax the radial artery, which may cause a temporary burning sensation 
in the hand and arm. Blood thinners are also administered to help prevent the formation of blood 
clots within the artery. Then the catheters will be moved through the tube and guided to the 
heart. A coronary angiogram and, if required, stent placement may be performed. After the 
completion of the procedure, the catheters and tubes will be removed from the radial artery. An 
inflatable balloon type device will be placed on your wrist to help stop bleeding. If cardiac 
catheterization is unsuccessful by transradial approach, a transfemoral approach may be used to 
complete the cardiac catheterization based on your provider’s clinical judgment. 
EXPLANATION OF TERMS 
• Cardiac Catheterization is a procedure that involves passing small catheters through 
your blood vessels in wrist or groin and injecting contrast dye to study the heart chambers 
(Ventriculogram) or blood vessels supplying the heart (Coronary Angiogram).  
• Coronary Angiogram is a study of blood vessels supplying the heart (Coronary 
arteries). It is done by injecting contrast dye into the blood vessels and studying them 
with fluoroscopy (A type of imaging study using Xrays). It helps to identify any 
blockages in the blood vessels supplying the heart. A significant blockage in these 
arteries can be the cause of chest pain (angina) or heart attack (myocardial infarction). 
• Ventriculogram is a study of ventricle (heart chamber). It involves injecting dye into the 
heart chamber and studying its size, shape and function using fluoroscopy. 
• Transfemoral: Traditionally cardiac catheterization has been done by passing small 
catheters through the blood vessel in the groin called the Femoral artery. This is called 
the Transfemoral approach. 
• Transradial: Cardiac catheterization can also be done by passing small catheters through 
the blood vessel in the wrist called the Radial artery. This is called the Transradial 
approach. Compared to transfemoral approach, transradial approach has less 
complications and patient comfort is more. When performed by providers experienced in 
transradial approach it is generally considered safer than transfemoral approach. In about 
5-10% of the patients, transradial approach can be unsuccessful and a transfemoral 
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WHAT ARE MY OTHER CHOICES IF I DO NOT TAKE PART IN THIS 
STUDY? 
If you decide not to take part in this study you may choose to have the usual approach described 
above. 
WHY IS THIS RESEARCH STUDY BEING DONE? 
The purpose of this study is to improve the success of cardiac catheterization by transradial 
approach and increase patient comfort by reducing radial artery spasm. Transradial approach 
chosen by your provider improves patient comfort and reduces bleeding complications 
significantly compared to the transfemoral approach (using the artery in the groin). Since the 
radial artery is smaller than the femoral artery, it is more prone to spasm. Cardiac catheterization 
by transradial approach may be difficult in some patients and they may need a switch to 
transfemoral approach to complete the procedure.  
This study is designed to look at the possibility of using topical nitroglycerine, a vasodilator, to 
increase the radial artery size and reduce radial artery spasm. This may: 
• increase patient comfort;  
• improve success of the transradial approach; and  
• avoid the need for switching to transfermoral approach. 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
There will be up to 300 people taking part in this study. 
WHAT ARE THE STUDY GROUPS? 
If you decide to take part in the study, in addition to the above mentioned usual treatment, you 
will receive topical lidocaine ointment, a local anesthetic (numbing cream), applied on your wrist 
one hour before the procedure. This may reduce pain felt during the lidocaine injection given as 
part of usual approach. Additionally, based on your random study assignment you will receive 
either topical nitroglycerine ointment (a vasodilator) or placebo applied to your wrist. The 
nitroglycerine may increase size of the radial artery and potentially improve the success of the 
procedure as well as your comfort during and after the procedure. 
EXPLANATION OF TERMS 
• Local anesthetic is a medication that acts locally on the nerves and blocks pain 
sensation. This is generally used during procedures involving manipulation of skin and 
superficial tissues to ensure patients do not experience pain or discomfort during the 


 
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procedure. It can be in the form of an ointment applied to the skin or a solution injected 
into the skin and tissues immediately below the skin. 
• Vasodilator is a medication that dilates blood vessels. 
You will be randomly assigned to one of two groups:   
1. Treatment group: Will receive a combination of topical lidocaine and topical 
nitroglycerine applied to the wrist while waiting in the holding area.  
2. Placebo group: Will receive a combination of topical lidocaine and placebo applied to the 
wrist while waiting in the holding area.  
This is a double-blind study; neither you nor your doctor will know what group you are in.  After 
informed consent is obtained, you will be randomized to the treatment group or placebo group.  
Patients and physicians will be blinded to the administered drug (topical nitroglycerine vs. 
placebo). 
• Randomization is a standard procedure used in clinical trials where subjects are assigned 
by chance to one study group or another.  It is used to make sure that the results of the 
study are not influenced by the selection of subjects/patients in one group as compared to 
the other.  This is important to make certain that study results are accurately interpreted 
and therefore beneficial to future patients.  In this study, you have a 50:50 chance of 
being assigned to one group or another.   
• Double Blinding is a process used in clinical trials where neither the person giving the 
treatment [doing the research] nor the patient [research subject] knows which treatment 
the patient [research subject] is receiving, or which group the research subject is 
participating in.  It is used in order to make sure that the subject and the person giving the 
treatment are not influenced by knowledge of the type of treatment that is being used. 
• Placebo is an inactive substance (with no drug in it, often called a “sugar pill” or 
“dummy pill”) that is compared to a drug in a clinical trial to see if the drug has a real 
effect.  A placebo is often used in clinical trials in order to “blind” the study so that the 
doctor and the subject cannot be influenced by his/her expectations of the effects of the 
drug.  The study can be “un-blinded” in case of an emergency. 
WHAT WILL HAPPEN IF I TAKE PART IN THE STUDY? 
Once you agree to participate in the study, you will receive all the standard treatment for cardiac 
catheterization by transradial approach, as described above. 
On the day of the procedure you will report to Ambulatory Cardiac Unit (Same Day Unit) 
opposite to Cardiac Catheterization Lab in the Bedford building.  


 
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As part of standard care, nurses will do the routine pre-procedure evaluation including vital 
signs, verifying lab data, etc.  
As part of the research study a brief ultrasound exam of your radial artery (wrist artery) will be 
done to measure its size. You will answer a brief 6 question survey to assess your anxiety level 
before the procedure. Based on the randomized assignment of your treatment, a combination of 
topical lidocaine (local anesthetic) and nitroglycerine or placebo will be applied to your wrist at 
least 60 minutes before the procedure. 
You will be transferred to the Cardiac Catheterization Lab and the procedure will be done as per 
standard approach described above. As part of the research study a repeat ultrasound exam of 
your radial artery (wrist artery) may be done immediately before the beginning of the procedure. 
HOW LONG WILL I BE IN THIS STUDY? 
You will be part of the study from the time of consent and enrollment, which will take place 
during your office visit or in the ambulatory cardiac unit (same day unit), until discharge from 
the Cardiac Catheterization Lab or admission to the inpatient unit after completion of the 
procedure. If you are hospitalized after your procedure, your participation will end 120 minutes, 
or 2 hours, after the removal of the TR band or comparable product, which is a compression 
band placed on your wrist during the procedure.  
WHAT EXTRA TESTS WILL I HAVE IF I TAKE PART IN THIS STUDY? 
An extra test necessary for this study is the measurement of the size of your radial artery (wrist 
artery) with a portable ultrasound device. This is a brief noninvasive test done bedside and 
involves no risk of injury or pain. 
WHAT POSSIBLE RISKS CAN I EXPECT FROM TAKING PART IN 
THIS STUDY? 
There are minimal risks associated with this study such as a drop in your blood pressure and 
headache. The drop in blood pressure should be mild and easily reversed with removal of the 
medication and or administration of intravenous (IV) fluids. The risk of drop in blood pressure is 
lower with topical nitroglycerine compared to the risk with intraarterial nitroglycerine (directly 
into the artery) given to all patients (both patients enrolled and not enrolled in the study) as part 
of standard approach. If headache occurs, the patient will be given acetaminophen (Tylenol) for 
relief. 
Pregnancy, Breastfeeding Women, Women of Childbearing Potential, and Contraception 
Women who are pregnant or nursing a child cannot participate in this trial.  You must confirm, to 
the best of your knowledge, that you are not now pregnant, that you do not intend to become 


 
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pregnant, and that you will use highly effective methods of contraception during study treatment.  
Highly effective methods of contraception include:   
• Total abstinence 
• Barrier methods of contraception 
• Use of oral, injected, or implanted hormonal methods of contraception or other forms of 
hormonal contraception that have comparable efficacy 
• Placement of an intrauterine device (IUD) or intrauterine system (IUS) 
• Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy) or tubal ligation before taking study treatment.   
• Male sterilization (prior to screening). 
 
If you suspect being pregnant during study treatment, you must inform the Study Doctor 
immediately.  You will not be allowed to receive study treatment if you are pregnant. 
WHAT POSSIBLE BENEFITS CAN I EXPECT FROM TAKING PART IN 
THIS STUDY? 
Taking part in this study may or may not provide additional benefits. 
The treatment group to which you are assigned may prove to be more effective and/or have 
fewer side effects than the other treatment group(s). 
Both treatment and control groups will receive topical lidocaine and you may  
• feel less or no pain at the time of lidocaine injection. 
Patients in the study group will receive topical nitroglycerine and it may 
• improve your comfort during the procedure,  
• improve the success of the procedure, and/or  
• reduce the need for changing to transfemoral (groin) approach. 
CAN I STOP TAKING PART IN THIS STUDY? 
Yes.  You can decide to stop at any time.  If you decide to stop for any reason, it is important to 
let the study doctor know as soon as possible so you can stop safely.  Even if you decide not to 
continue in the study, no therapy will be withheld, and you will still receive standard treatment, 
follow–up, and clinical monitoring.  In addition, no changes will be made with regard to 
confidentiality and release of medical information. 


 
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The study doctor will tell you about new information or changes in the study that may affect 
your health or your willingness to continue in the study. 
WHAT ARE MY RIGHTS IN THIS STUDY? 
Taking part in this study is your choice.  No matter what decision you make, and even if your 
decision changes, there will be no penalty to you.  You will not lose medical care or any legal 
rights.   
If you have any questions about YOUR RIGHTS AS A RESEARCH SUBJECT, contact the Aultman 
Health Foundation Human Research Review Board in the Office of Research, 2600 Sixth Street 
SW, Canton, Ohio   44710 [330-363-6793] [e-mail: 
HumanResearch.ReviewBoard@aultman.com].  You may also contact them if you feel under 
any pressure to enroll or continue to participate in this study. 
WHAT ARE THE COSTS OF TAKING PART IN THIS STUDY? 
It is expected that you will not have any additional costs to participate in this study.  You will 
receive topical lidocaine and topical nitroglycerine (or placebo) at no charge.  Any tests that are 
outside the standard of care will be covered by research.  All costs not related to the study, 
including those related to the standard treatment of your disease will be your responsibility. 
You will not be paid for taking part in this study. 
WHAT HAPPENS IF I AM INJURED OR HURT BECAUSE I TOOK PART 
IN THIS STUDY? 
If you feel you have been injured or hurt as a result of taking part in the study, it is important that 
you contact 24 hour emergency number at 330-454-8076 immediately.  You will get medical 
treatment if you are injured or hurt as a result of taking part in this study. 
Immediate and necessary care for research-related adverse events will be provided at Aultman 
Hospital if you are injured because of participation in this research project.  Any costs associated 
with providing this care not paid for by your insurance will be your responsibility.  Aultman 
Hospital has not arranged to provide compensation for any injury you may suffer as a direct 
consequence of the non-negligent performance of the procedures described above.  However, by 
signing this form, you do not give up your right to seek payment for harm you receive while 
participating in this study. 
WHO WILL SEE MY MEDICAL INFORMATION? 
Your privacy is very important to us and the researchers will make every effort to protect it. 
Your information may be given out if required by law. For example, certain states require 
doctors to report to health boards if they find a disease like tuberculosis. However, the 


 
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researchers will do their best to make sure that any information that is released will not identify 
you. Some of your health information, and/or information about your specimen, from this study 
will be kept in a central database for research. Your name or contact information will not be put 
in the database. 
There are organizations and individuals that may inspect your records.  These organizations and 
individuals are required to make sure your information is kept private.  Some of these 
organizations and individuals are: 
• 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  
WHERE CAN I GET MORE INFORMATION? 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 
WHO CAN ANSWER MY QUESTIONS ABOUT THIS STUDY? 
You can talk to Dr. Prabhakaran Gopalakrishnan, the Principal Investigator, about any 
questions or concerns you have about this study or to report side effects or injuries. Contact Dr. 
Prabhakaran Gopalakrishnan at the telephone number and address listed on the first page. 
If you have any questions about COMPENSATION OR MEDICAL TREATMENT FOR RESEARCH-
RELATED INJURIES contact the Aultman Health Foundation Human Research Review Board in the 
Office of Research, 2600 Sixth Street SW, Canton, Ohio   44710 [330-363-6793] [e-mail:  
HumanResearch.ReviewBoard@aultman.com] 
If you have any questions about YOUR RIGHTS AS A RESEARCH SUBJECT, contact the Aultman 
Health Foundation Human Research Review Board in the Office of Research, 2600 Sixth Street 
SW, Canton, Ohio   44710 [330-363-6793] [e-mail:  
HumanResearch.ReviewBoard@aultman.com].  You may also contact them if you feel under 
any pressure to enroll or continue to participate in this study. 


 
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Authorization to Use and/or Disclose (Release) 
Individually Identifiable Health Information for 
Research Purposes 
You have rights regarding the privacy of your medical information collected prior to and in the 
course of this research study.  These rights are protected by a federal law that requires the 
Aultman Health Foundation and its affiliated hospitals and clinics, researchers, health care 
providers and physicians (collectively, “Aultman”) to protect the privacy of information that 
identifies you and relates to your past, present, and future physical and mental health and 
conditions (“protected health information”).   
Before researchers use or share any health information about you as part of this study, Aultman 
is required to obtain your authorization.  This Authorization helps explain to you how this 
information will be used or shared with others involved in the study.   
• The Aultman Health Foundation and its hospitals, clinics, health-care providers and 
researchers are required to protect the privacy of your health information.   
• You should have received a Notice of Privacy Practices when you received health care 
services here.  If not, let us know and a copy will be given to you.  Please carefully 
review this information.  Ask if you have any questions or do not understand any parts of 
this notice. 
• If you agree to take part in this study your health information will be used and shared 
with others involved in this study.  Also, any new health information about you that 
comes from tests or other parts of this study will be shared with those involved in this 
study. 
• Health information about you that will be used or shared with others involved in this 
study may include your research record and any health care records at Aultman.  For 
example, this may include your medical records, x-ray or laboratory results.  
Psychotherapy notes in your health records (if any) will not, however, be shared or used.  
Use of these notes requires a separate, signed authorization. 
• If you decide to participate in this research study, your protected health information will 
be used and shared with others as explained below. 
Purpose of Use and/or Disclosure of Health Information 
By signing this form, you are giving permission to Aultman Health Foundation, Aultman 
Hospital, Cardiovascular Clinical Trials, and all other Aultman Health Foundation affiliated 


 
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health care provider organizations to use and/or disclose your health information that 
individually identifies you for the purposes of the research study (“Study”) listed above. 
What Health Information May be Used and/or Disclosed? 
To do this research study, we need your permission to collect and use some of your health 
information, or you cannot be in the study.  This information may come from questions we ask, 
forms we ask you to fill out, or your medical record, as described below.  We will only collect 
and use information needed for the study.   
Aultman may use and/or disclose your past, present and future records and information as 
described in the study protocol approved by the Human Research Review Board which may 
include: 
• Lab test results (which 
may include genetic 
tests, HIV/AIDS tests 
and/or tests for other 
communicable diseases 
if part of my records) 
• Procedure reports 
• Hospitalization records 
• Operative reports 
• Outpatient/Office visits, 
exams, consultations, phone 
call records and notes 
• Radiology/x-ray images 
and/or reports 
• Registration and billing 
information 
• Emergency room reports 
• Medication information 
including drugs, vitamins, 
and herbal remedies 
• Questionnaires and diaries 
• Pathology reports 
• Other (describe):        
 
Why will protected health information [PHI] about me be used or shared with 
others? 
The main reasons include: 
• To conduct and oversee the research described in the consent document and for all 
purposes necessary to conduct and ensure the integrity of the study. 
• To ensure the research meets legal, institutional, and accreditation requirements; and 
• To conduct public health activities (including reporting of adverse events or situations 
where you or others may be at risk of harm). 
Other reasons may include for treatment, payment or health care operations.  For example, some 
medical information produced by this study may become part of your hospital medical record 
because the information may be necessary for your medical care. 


 
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Who will use or share protected health information about me at the Aultman 
Health Foundation 
Those who oversee the study will have access to your information, including: 
• Researchers and staff at Aultman will use, share and receive your personal health 
information for this research study.  They will make every reasonable effort to protect the 
information and keep it confidential.   
• The only Aultman Hospital employees allowed to handle your health information are 
those on the study team, and those on the Aultman Human Research Review Board, the 
committee that oversees research at Aultman, and Aultman officials who review the 
research plan and check the research activities to make sure the hospital’s rules are 
followed. 
• Authorized Aultman staff not involved in the study may be aware that you are 
participating in a research study and have access to your information.  If this study is 
related to your medical care, your study-related information may be placed in your 
permanent hospital, clinic or physician’s office records.  As a result, this research 
information may be seen by authorized members of the Aultman workforce who need to 
access your medical record in the performance of their duties (for example, to provide 
treatment, to ensure integrity of the research, accounting or billing matters, etc.) 
Will my protected health information be shared with people outside the 
Aultman Health Foundation? 
We may share your information with people who do not work at Aultman Hospital because they 
planned this study, pay for this study, or work with us on this study.  The federal Privacy Rule 
may no longer protect your health information once it leaves Aultman Hospital.  Once your 
health information has been disclosed, the information may no longer be protected under the 
laws and regulations that apply to Aultman.  The recipients may share the information with 
others without your permission, if permitted by laws governing them. 
There are organizations that may inspect your records for quality assurance and data analysis.  
These organizations are required to make sure your information is kept private, unless required 
by law to provide information.  For this study, we plan to share information with those doctors, 
researchers or government representatives working with us on this study at the institutions or 
companies listed here: 
Your health information may also be shared with federal and state agencies that have oversight 
of the study or to whom access is required under the law.  These may include: 
• The Food and Drug Administration (FDA). 


 
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How long will protected health information about me be used or shared with 
others? 
If you sign this form, we plan to keep your information for 10 years after the research study ends 
in case we need to check it again for this study. 
We will not use your health information for a different study without your permission, or the 
permission of the Aultman Human Research Review Board.  Once all personal identification is 
removed, the information might be used or released for other purposes without asking you. 
May I have access to my medical information that results from my 
participation in this research study? 
In accordance with the Aultman Health Foundation Notices of Privacy Practices document that 
you have been provided, you are permitted access to information (including information 
resulting from your participation in this research study) contained within your medical records 
filed with your health care provider. 
During your participation in this study, you will have access to your medical record and any 
study information that is part of that record. 
Statement of Privacy Rights 
If you change your and later and do not want us to collect or share your health information, you 
need to send a letter to the Principal Investigator at the mailing address on the first page.  The 
letter must say that you have changed your mind and do not want the researcher to collect and 
share your health information.  If you change your mind and revoke the authorization, you will 
not be allowed to continue to participate in the Study. 
If you revoke this authorization, Aultman may not continue to use and/or disclose your health 
information for this Study, except that: 
• Your health information that has already been disclosed before you revoked this 
Authorization cannot be taken back; and 
• Aultman and the recipients may continue to use and disclose your health information 
already collected for this research Study for the purposes of maintaining the integrity of 
the Study, and for regulatory compliance. 
You have the right to limit the use and sharing of your PHI, and you have the right to see your 
medical records and know who else is seeing them. 


 
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You have the right to refuse to sign this authorization.  You do not have to give this permission 
for use of your PHI.  If you decide not to provide permission, you will not be able to participate 
in this research study.  Your health care outside of the study, payment for your health care, and 
your health care benefits will not be affected if you choose not to sign this form.   
Publication of results or use for teaching purposes 
The information from this study may be published in scientific journals or presented at scientific 
meetings but your identity will be kept strictly confidential.  Your name or other identifiers will 
not be used in any publication or teaching materials without your specific permission. 


 
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CONSENT TO PARTICIPATION IN TNT-RASP 
By signing my name below, I confirm the following 
• I have read (or had read to me) this entire consent document.  All of my questions 
have been answered to my satisfaction. 
• The study’s purpose, procedures, risks and possible benefits have been explained to 
me.   
• I agree to let the study team use and share the health information and other 
information gathered for this study. 
• I voluntarily agree to participate in this research study.  I agree to follow the study 
procedures as directed.  I have been told that I can stop at any time. 
IMPORTANT:  You will be given a copy of this signed document for your records.  A second 
copy will be kept together with the Investigator’s research records on this study.  A third copy 
will be placed in your Aultman Hospital medical record. 
Please keep it where you can find it easily.  It will help you remember what we discussed today 
Research Participant’s Name [PRINT]: 
Research Participant’s Signature: 
Date/Time 


 
TNT-RASP Protocol [Version 3, Amendment 2; 14-Jul-2016] 
Consent Document Version: 3.0; 14-Jul-2016 
Approved by HRRB:   07-Sep-2016 
Page 17 of 17 
INVESTIGATORS CONFIRMING STATEMENT 
I have given this research subject information on the study, which in my opinion is accurate and 
sufficient for the subject to understand fully the nature, risks and benefits of the study, and the 
rights of a research subject.  There has been no coercion or undue influence.   
INVESTIGATOR/INDIVIDUAL OBTAINING CONSENT 
Date/Time 
I have explained the purpose of the research, the study procedures, identifying those that are 
investigational, the possible risks and discomforts and potential benefits.  I have answered any questions 
regarding the research study to the best of my ability.