A Prospective, Multi Center Pilot Study Evaluating Plaque Photoablation Using the RA-308 Excimer Laser in Subjects With Symptomatic Infrainguinal Lower Extremity Vascular Disease
Phase: NA
Conditions: Peripheral Arterial Disease
Sponsor: Ra Medical Systems

 
 
 
 
A Prospective, Multi Center Pilot Study Evaluating Plaque 
Photoablation Using the RA-308 Excimer Laser in Subjects with 
Symptomatic Infrainguinal Lower Extremity Vascular Disease 
 
 
 
 
Protocol: RMS-102 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sponsor: 
Ra Medical Systems, Inc. 
1930 Kellogg Avenue 
    Carlsbad, CA 92008 
 
 
  
 
CONFIDENTIALITY STATEMENT 
 
This document contains proprietary information that is privileged or confidential and subject to terms of the Non-Disclosure 
Agreement. No portion of this work may be reproduced in whole or in part without the express written permission of Ra Medical 
Systems. Persons to whom the information is disclosed must be informed that this and future information is privileged or 
confidential.  

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 2 
 
A Prospective, Multi Center Pilot Study Evaluating Plaque Photoablation Using the RA-308 
Excimer Laser in Subjects with Symptomatic Infrainguinal Lower Extremity Vascular Disease 
 
 
 
 
Protocol: RMS-102 
 
January 11, 2016 
 
 
 
 
 
I have read this protocol and agree to conduct the study as outlined herein. 
 
 
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this study. I will discuss this material with them to ensure they are 
fully informed regarding the device and the conduct of the study. 
 
 
 
 
 
______________________________________________________________________ 
Principal Investigator’s Signature 
 
 
 
 
Date 
 
 
 
______________________________________________________________________ 
Name of Principal Investigator (Typed or Printed) 
 
 
 

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 3 
TABLE OF CONTENTS 
 
SYNOPSIS………………………………………………………………………………….…..4 
 
Patient Informed Consent Form.................................................................................... 19 
 
 
APPENDIX A:   Informed Consent 
APPENDIX B:   Case Report Forms 
APPENDIX C:   Declaration of Helsinki  
 

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 4 
A Prospective, Multi Center Pilot Study Evaluating Plaque Photoablation Using the RA-308 
Excimer Laser in Subjects with Symptomatic Infrainguinal Lower Extremity Vascular Disease 
 
 
SYNOPSIS 
 
 
Study Objective 
To evaluate the safety and efficacy of the RA-308 Excimer Laser 
System and DABRA Catheter for treating subjects with symptomatic 
infrainguinal lower extremity vascular disease with chronic total 
occlusions that cannot be crossed with standard guide wires. 
 
Study Device 
The RA-308 Excimer Laser System and DABRA 101 Catheter consists 
of a 308 nanometer wavelength Excimer laser and a fluid filled optical 
catheter. 
 
Study Design 
A multi-center, prospective, non-randomized, open-label study. The 
study will conducted at a minimum of two sites. 
 
 
Sample Size 
Up to 50 male and female subjects will be enrolled.   
 
 
Outcome Measures  Procedural success, defined as crossing the target lesion based on 
angiographic analysis at the time of the procedure. Crossing the target 
lesion is defined as successfully placing any endovascular device distal 
to the occlusion. 
 
No device related major adverse events. 
 
STUDY POPULATION 
 
Inclusion Criteria 
Subjects must satisfy the following criteria before entering the study: 
• 
Signed informed consent obtained. 
• 
Symptomatic infrainguinal lower extremity vascular disease (Rutherford category 3, 
4, 5 or 6), stable for at least 2 weeks prior to study inclusion. 
• 
Lesions in the superficial femoral artery (SFA), popliteal, infrapopliteal or tibial 
arteries  
• 
At least one angiographically identifiable infrageniculate artery 
• 
Patients must be poor surgical candidates, indicated by at least one of the following 
conditions: 
• Absence of venous autologous grafts (that is, lack of a suitable vein to use for 
bypass) 
• Poor (diffusely diseased or ≤1mm diameter) or no distal vessels available for 
graft anastamosis 

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 5 
• High risk of surgical mortality, evidenced by American Society of 
Anesthesiologists  Physical Class 4 or higher 
• 
Have a lesion that is a chronic total occlusion that cannot be crossed with a standard 
guidewire. NOTE: This can only be determined at the time of the procedure. 
 
Exclusion Criteria 
Potential subjects who meet any of the following criteria will be excluded from participating 
in the study: 
• 
Age below 18 years 
• 
Pregnancy, or plan to become pregnant 
• 
Participation in another cardiovascular or peripheral vascular IDE study 
• 
Myocardial infarction (MI) in prior month  
• 
Stents at treatment site 
• 
Disorders or allergies precluding use of radiographic contrast 
• 
Renal insufficiency severe enough to contraindicate use of radiographic contrast 
• 
Contraindication to treatment with anticoagulants 
• 
Untreated ipsilateral iliac stenosis >70% 
• 
Inability or unwillingness of the patient to comply with intended examinations. 
• 
Unavailability of required procedural or imaging equipment 
• 
Lesion located in a graft 
• 
Hemodynamically significant arrhythmia or left ventricular ejection fraction <20% 
• 
Life expectancy less than 6 months 
• 
Necrosis necessitating major amputation 
• 
Unwillingness of the patient to be anti-coagulated 
 
Time and Events Schedule 
 
Event 
Screening 
(Visit 1) 
Procedure 
(Visit 2) 
Follow-Up 
 
 
Day 0 
≥30 Days 
Demographics and Medical History 
Review 
x 
 
 
Ankle-Brachial Index (ABI) 
x 
 
As needed 
Rutherford Classification 
x 
 
 
Angiography  
 
x 
 
Crossing Procedure 
 
x 
 
Device-Related Safety Data 
 
As needed 
As needed 
Doppler Ultrasound 
 
 
As needed 

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 6 
1.0 
INTRODUCTION 
 
1.1 
Background 
The distribution of Peripheral Artery Disease (PAD), including Chronic Total Occlusions 
(CTOs), varies with multiple factors, such as age and the presence of cardiovascular risk 
factors. Aortoiliac disease is associated with young age, females, and current smokers. 
Femoropopliteal involvement in occlusive PAD is extremely common and, in one series, 
was present in 80% of symptomatic patients undergoing angiography. The predilection of 
disease in this segment may be due to its conduit-like nature, with no or few major 
branches, and torsion or stretching resulting from limb movement. These characteristics 
may cause relatively more damage of the vaso vasorum and endothelium than other limb 
segments, leading to accelerated atherosclerosis. Additionally, the flow characteristics 
following the development of a stenosis may promote long occlusions. Infrapopliteal 
disease is associated with diabetes mellitus, and diffuse and occlusive disease is common. 
Despite the complex nature of infrapopliteal disease, endovascular techniques have 
acceptable limb salvage rates. This approach, therefore, may be increasingly used for CTOs 
in patients with limited surgical options, due to co-morbidities or lack of bypass conduits or 
target vessels. Overall, CTOs are more the norm than the exception in PAD. The decision to 
attempt percutaneous revascularization of CTOs depends on many factors, such as severity 
of symptoms, and lesion characteristics, including location, calcification and length, and 
operator experience and institutional availability of the specialized devices. 
 
From 1975-1979 many scientists and institutions worked on the initial development of a 
family of gas lasers known as the "excimer." Those pioneers were with institutions 
including Lumonics, Lambda Physik, Avco, and Caltech. The development was initiated in 
part because of the short wavelength of this type of light source. Monochromatic short 
wavelength sources were thought to have a variety of commercial and military applications. 
The name excimer is a contraction of "Excited Dimer," a description of a diatomic molecule 
in which the component atoms are bound in the excited state, but not in the ground state.  
The important gas molecules are rare gas halides including argon fluoride, krypton fluoride, 
and xenon chloride.  
The ultraviolet light from an excimer laser is well absorbed by biological matter and organic 
compounds. Rather than burning or cutting material, the excimer laser adds enough energy 
to disrupt the molecular bonds of the surface tissue, which effectively disintegrates in a 
tightly controlled manner through ablation rather than burning. Thus excimer lasers have the 
useful property that they can remove exceptionally fine layers of surface material with 
almost no heating or change to the remainder of the material which is left intact. These 
properties make excimer lasers well suited to precision micromachining organic material, or 
delicate surgeries such as eye surgery. At lower energy densities, the laser may also be used 
for dermatological disorder treatment. 
Excimer laser light is typically absorbed within the first billionth of a meter (nanometer) of 
tissue. In the early 1980s, researchers at IBM’s T. J. Watson Research Center observed the 
effect of the ultraviolet excimer laser on biological materials. They found that the laser 
made clean precise cuts that would be ideal for delicate surgeries. Subsequent work 
introduced the excimer laser for use in angioplasty or atherectomy, destroying blockages in 
arteries using molecular ablation. Xenon chloride excimer lasers, having a wavelength of 

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 7 
308nm, can also treat a variety of dermatological conditions including psoriasis, vitiligo, 
atopic dermatitis, and leukoderma. 
 
In the late 1980s, 308nm excimer laser atherectomy was developed as an alternative method 
of percutaneous angioplasty, with the objective of reducing the high rate of restenosis 
associated with other angioplasty or stenting techniques. Excimer laser atherectomy is a 
procedure that utilizes an intravascular catheter system to deliver high-energy pulsed laser 
light to atherosclerotic lesions, or plaque, that are causing stenosis or occlusion of native 
arteries, or intra-arterial stents, while producing relatively little thermal damage to the 
vessel wall. The pulses vaporize thin sections of tissue without causing significant damage 
to surrounding tissue. It is thought that reduction of plaque using laser ablation could be 
more effective in enlarging the vessel lumen than balloon angioplasty alone. Early data 
from large observational registry studies published in the early 1990s provided evidence of 
the safety of the procedure. By 1994, Advanced Interventional Systems (AIS) had 
commercialized a system and gained FDA approval for the procedure. Later in the decade 
AIS merged with Spectranetics, Inc., which had developed an excimer for treating 
peripherals. There are approximately 1,000 Spectranetics lasers placed today, and thousands 
of excimer laser endovascular procedures are performed each year. 
 
The Ra Medical team, which includes members of the Spectranetics and AIS development 
teams, began developing the RA-308 Excimer Laser System and DABRA Catheter for 
crossing lesions in 2006, after the successful launch of the PHAROS EX-308 excimer laser 
phototherapy system. 
 
1.2 
Alternative Treatments and Methods 
Patients that have agreed to participate in the study and meet the inclusion criteria and have 
signed the informed consent form and present on the day of treatment for the endovascular 
diagnostic procedure will be considered for the study. It is at this point when it will be 
determined that the patient meets all of the inclusion criteria. If the patient’s lesion can be 
crossed with a guide wire or if the physician feels that other options are more appropriate 
for the patient, the patient will be treated with the laser catheter and not be included in the 
study. 
  
There are several commercially available CTO crossing methods and atherectomy systems 
on the market today. These include standard guide wire manipulation. Standard guide wire 
recanalization should initially be attempted, even for long, occlusive lesions. Although the 
inability to remain intraluminal or re-enter the true lumen distally are the main reasons for 
failure of this technique, there is still a relatively high chance of success. For aortoiliac 
lesions, an ipsilateral retrograde femoral approach is usually the simplest, but an alternative 
approach from contra lateral femoral or brachial access may be needed. For superficial 
femoral artery (SFA) lesions, a contra lateral femoral approach with a crossover sheath is 
usually needed, but for more distal lesions, such as infrapopliteal, an ante grade femoral 
approach may be preferable, so that device torquability and push ability is optimized.  
 

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 8 
1.3 
Rationale for the RA-308 Excimer Laser System 
The RA-308 Excimer Laser system may cross calcified lesions without subluminal 
penetration, common when using the standard guide wire approach. Additionally, the 
energy delivered within the patient with the excimer laser is much lower than when using 
mechanical surgical methods. This may result in less vascular trauma and may improve the 
clinical outcome for the patient. 
 
1.4 
Previous Clinical Experience 
The RA-308 Excimer Laser System and DABRA Catheter have been used on three patients 
to date. Their peripheral vascular blockages were ablated (crossed) and the patients were 
then treated with balloon angioplasty. There were no adverse events and the procedural 
outcomes were excellent.   
 
1.5 
Risk Analysis 
We believe that the procedure does not pose a significant risk to the patient. The patients are 
likely candidates for amputation. In addition, the procedure does not pose additional risk to 
the patient because of the following: 
 
• The endovascular procedure will occur anyway, regardless of whether or not the laser is 
used. This endovascular procedure is used to help diagnose the precise nature of the 
disease, the location of any stenosis, and treatment will be initiated with common 
endovascular tools, such as guidewires and balloons. The DABRA laser catheter will be 
attempted only after these tools fail or if the physician determines that there is no other 
option. 
• The catheter does not present a potential for serious risk to the health, safety, or welfare 
of the subject, because they already have a high probability of amputation. In addition, 
the potential adverse events related to the DABRA catheter have low risk to these 
patients. Perforation is easily mitigated and repaired with a tamponade technique, and 
embolism or debris from any of these procedures is likely to be filtered downstream by 
the narrowing of the vasculature.  
• The catheter is not implanted, and is not of substantial importance in treating the 
disease. It only crosses the lesion to allow therapeutic treatment. It is a small part of a 
much more complicated procedure. The energy delivered by the DABRA catheter is 
orders of magnitude less than other technologies, including mechanical, barometric, 
radiofrequency, and ultrasonic or sonic. 
• All endovascular interventionalists have the skill and training to use this device safely. 
Excimer lasers have been used for over 20 years, and their operation is no more difficult 
than using a stand alone guide wire. The only difference is depressing the footswitch.  
 
2.0 
STUDY OVERVIEW 
 
2.1 
Study Design 
The study is a multi center, prospective, non-randomized, open-label study conducted at two 
investigational centers in the US, one in southern Mississippi and one in southern 
California, with at least two operators at each site. 50 subjects can be enrolled. Follow-up 

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 9 
occurs at the end of the procedure in the form of an angiogram to determine if the lesion 
was crossed. Additional follow-up may not necessary because of the binary nature of the 
crossing, and also because any future follow-up would be assessing the effectiveness of 
adjunct therapy, e.g. balloon angioplasty. Long term results are entirely dependent on this 
subsequent treatment. Because the DABRA crosser only allows adjunct devices to be used, 
30-day follow-up measuring the performance of the adjunct therapy might affect the 
physician’s choice of therapy, and compromise the patient’s treatment. Therefore, 30-day 
follow-up, which evaluates the effectiveness of the adjunct therapy, might raise ethical 
concerns. 
 
However, the follow-up can be done by ABI, Doppler ultrasound, auscultation, or by 
discussion of the level of claudication and motion pain with the patient. 
 
2.2 
Study Objectives 
To evaluate the safety and efficacy of the RA-308 Excimer Laser System and DABRA 
Catheter for treating subjects with symptomatic infrainguinal lower extremity vascular 
disease with chronic total occlusions that cannot be crossed with standard guide wires, or 
lesions where an attempt to cross would, in the opinion of the interventionalist, result in 
either a subintimal path or a perforation. 
 
2.2.1 Outcome Measures 
 
Procedural success, defined as crossing the target lesion based on 
angiographic analysis. Crossing the target lesion is defined as successfully 
placing any endovascular device distal to the occlusion. 
 
No device related major adverse events 
 
3.0 
STUDY POPULATION 
3.1 
General Considerations 
Subjects will undergo baseline evaluation to determine eligibility for the study. Subjects 
who do not meet the entry criteria are considered screening failures. Case report forms do 
not need to be completed for screening failures; however, a record for each patient screened 
and the reason for screening failure must be indicated in the screening log. 
 
The investigator and/or designated study personnel are responsible for screening all 
potential candidates and selecting those who are appropriate study candidates as defined by 
the following inclusion and exclusion criteria.   
 
Signed informed consent will be obtained from the patient before any specific study 
procedures are undertaken. The patient will sign one original informed consent and a copy 
will be provided to them. The study requirements should be discussed with the patient with 
ample time provided for the consent review. All required parties (e.g., patient, witness, 
investigator or designee) should sign and date on the same consent as the patient.   

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 10 
3.2 
Inclusion Criteria 
Subjects must satisfy the following criteria before entering the study: 
 
• 
Signed informed consent obtained. 
• 
Symptomatic infrainguinal lower extremity occlusive vascular disease (Rutherford 
category 3, 4, 5 or 6), stable for at least 2 weeks prior to study inclusion. 
• 
Lesions in the superficial femoral artery (SFA), popliteal, or infrapopliteal arteries  
• 
At least one angiographically identifiable infrageniculate artery 
• 
Patients must be poor surgical candidates, indicated by at least one of the following 
conditions: 
 Absence of venous autologous grafts (that is, lack of a suitable vein to use for 
bypass) 
 Poor (diffusely diseased or ≤1mm diameter) or no distal vessels available for 
graft anastamosis 
 High risk of surgical mortality, evidenced by American Society of 
Anesthesiologists  Physical Class 4 or higher 
• 
Have a lesion that is a chronic total occlusion that cannot be crossed with a standard 
guidewire. NOTE: This can only be determined at the time of the procedure. 
 
3.3 
Exclusion Criteria 
Potential subjects who meet any of the following criteria will be excluded from participating 
in the study: 
• 
Age below 18 years 
• 
Pregnancy, or plan to become pregnant 
• 
Participation in another cardiovascular or peripheral vascular study 
• 
Myocardial infarction (MI) in prior month  
• 
Stents at treatment site 
• 
Disorders or allergies precluding use of radiographic contrast 
• 
Renal insufficiency severe enough to contraindicate use of radiographic contrast 
• 
Contraindication to treatment with anticoagulants 
• 
Untreated ipsilateral iliac stenosis >70% 
• 
Inability or unwillingness of the patient to comply with intended examinations. 
• 
Unavailability of required procedural or imaging equipment 
• 
Lesion located in a graft 
• 
Hemodynamically significant arrhythmia or left ventricular ejection fraction <20% 
• 
Life expectancy less than 6 months 
• 
Necrosis necessitating major amputation 
• 
Unwillingness of the patient to be anti-coagulated 
 
4.0 
STUDY DEVICE DESCRIPTION  
 
4.1 The RA-308 Excimer Laser System 
The RA-308 Excimer Laser System is a self-contained unit that connects to a sterile energy 
delivery catheter for use in vascular procedure under fluoroscopic guidance. The laser 

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 11 
energy is commanded by a footswitch that connects to a control system to generate and 
monitor the laser energy pulses. 
The laser energy is ultraviolet at 308nm and is delivered to the surgical site by the single-
use catheter that is used in conjunction with other catheter and vascular technology to 
complete the surgical system. 
The energy and density of the laser beam is sufficient to ablate tissue within 50µm of the 
tip. There is no significant off-axis radiation. 
The catheter is inserted into a patient’s peripheral vasculature through a previously inserted 
guiding support catheter, allowing the physician to deliver laser energy targeted to a 
blockage (lesion) in the blood vessel. Laser energy impinged on the blockage ablates, or 
debulks, the lesion material thus producing a channel through the blockage.   
 
4.2 Excimer Laser for Use in Plaque Photoablation 
 
Refer to the device Instructions for Use for a thorough description of the procedure. 
 
Procedure Description 
The excimer laser crossing procedure is performed in the Catheter Laboratory using 
standard endovascular techniques. Following introduction to the vascular system and 
diagnosis using fluoroscopy, including determining that a standard guidewire cannot cross 
the lesion, the following general guidelines are followed: 
1. Insert a commercial guide wire to the blockage.  
2. Pass an appropriate guiding catheter (support catheter) over the wire to the lesion. (Steps 
1 & 2 can be reversed depending on physician choice.) 
3. Remove the guide wire if one fails to cross the CTO or if, at the physician’s discretion, 
angiographic factors determine that a guide wire should not be used because of the presence 
of a rounded or eccentric stump might bias the guide to a subintimal route, or other 
complicating factor. 
4. Save the initial guide wire and insert the laser catheter and perform a stepwise crossing of 
the lesion.   
5. Cross the CTO with the laser catheter following the step-by-step procedure in the 
instructions for use.  
6. Exchange the laser catheter with the previous wire or another wire.   
7. Remove the guide catheter leaving the guide wire in place and, at the physician’s 
discretion, insert other endovascular devices to enhance blood flow. 
 

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 12 
5.0 
STUDY EVALUATIONS 
 
5.1 
Overview 
The visit schedule and procedures required by this protocol are summarized below: 
Event 
Screening 
(Visit 1) 
Procedure 
(Visit 2) 
Follow-Up 
 
 
Day 0 
≥30 Days 
Demographics and Medical History 
Review 
x 
 
 
Ankle-Brachial Index (ABI) 
x 
 
As needed 
Rutherford Classification 
x 
 
 
Angiography 
 
x 
 
Crossing Procedure  
 
x 
 
Device-Related Safety Data 
 
As needed 
As needed 
Doppler Ultrasound 
 
 
As needed 
 
5.2 
Screening 
Prior to any study-specific tests or procedure, the benefits and risks of the study must be 
explained and written informed consent must be obtained from the subject.   
 
 
The following tests and activities must be performed to verify eligibility: 
• Documentation of subject demographic information 
• Documentation of relevant medical history 
• Rutherford classification 
• Review of all inclusion/exclusion criteria to confirm subject eligibility 
 
5.3 
Procedure 
The following information will be collected for study subjects: 
• Pre-laser treatment stenotic assessment using angiography 
• Laser treatment procedure time  
• Post-laser treatment stenotic assessment using angiography 
• Adjunctive procedures, if any, as recommended by the physician  
• The duration of lasing 
• Device related safety data 
 
5.4 
Follow-Up (≥30 days) 
The following information may be collected: 
• Ankle-brachial index 
• Rutherford classification 
• Device-related safety data 
• Auscultation 
• Doppler ultrasound 
• Any other relevant information provided by the patient 

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 13 
 
6.0 
STATISTICAL METHODS 
 
6.1 
Primary Objective 
The primary objective of this study is to demonstrate that the Ra device meets its 
performance goal of a success rate in crossing vascular lesions of at least 65%. A 
study of the predicate device observed 37 successes in a trial of 47 patients, or a 
79% success rate with a 95% confidence interval of 65-88% (Wilson score interval). 
The performance goal for the Ra device is thus set to be a success rate of at least 
65% and the primary objective is to show that the Ra device exceeds this 
performance goal in a single-arm multi-site pivotal trial. Crossing success rate will 
be a binary endpoint, where successful crossing of a lesion is defined as crossing the 
target lesion based on angiographic analysis. 
6.2 
Statistical Methodology 
Primary Objective Test 
The primary objective will be tested with a one-sided exact binomial test using a 
significance level of 0.025. 
6.3 
Hypothesis 
The following null hypothesis will be tested with an overall significance level of 
0.025 
  H0: p ≤ 65% 
where  is the Ra device crossing success rate.  The alternative hypothesis is: 
  Ha: p > 65% 
6.4 
Study Design 
This study will be a non-randomized, single arm, prospective, multi-site clinical 
trial. The primary effectiveness endpoint will be evaluated using a one-sided test 
comparing the Ra device crossing success rate to the performance goal of 65%. The 
lower 95% confidence interval for the success rate of the predicate device was 65%. 
6.5 
Sample Size Rationale 
The required number of subjects to achieve 80% probability to demonstrate the Ra 
device meets the performance goal when the true success rate is 97% was calculated 
in the Power Analysis of One Proportion Procedure of NCSS Power Analysis 
Statistical Software (PASS), Version 14. A 97% success rate was observed in a trial 
of 78 patients using a similar device (Visona 1998). A sample size of 14 patients 
yields a 94% probability of meeting the PG of 65% crossing success when the true 
Ra device rate is 97%; the study will conclude that the PG has been met if 13 or 
more of the 14 patients are successes. A sample size of 50 patients yields a 99.99% 
probability of meeting the PG; the study will conclude that the PG has been met if 
40 or more of the 50 patients are successes.  
6.6 
Data Analysis 
The categorical data will be summarized descriptively with frequencies along with 
the associated percentages. The continuous variables will be summarized by number 
of subjects, mean, median, standard deviation, minimum and maximum. 
6.6.1 Adverse Events 

 
Ra Medical Systems Confidential, RMS-102               Clinical Protocol 05-203-84-10000102 R7                     Page 14 
The number of subjects with at least one adverse event will be tabulated.   
The number of subjects and the number of adverse events will be tabulated by 
severity and causality and relationship to the treatment procedure. 
7.0 RISK ANALYSIS 
7.1 
Summary of Potential Benefits 
The potential benefit of the RA-308 Excimer Laser System and DABRA Catheter is 
that occlusions in the vasculature may be crossed. Through an endovascular 
approach, the device may assist in improving blood flow to limbs and/or enable 
treatment with other devices and technologies.   
7.2 
Summary of Potential Risks 
Use of the RA-308 Excimer Laser System and DABRA Catheter may contribute to 
the following complications:  
  
Procedural Complications  
 Spasm 
 Major dissection 
 Thrombus 
 Distal embolization 
 Perforation 
 Other 
 
 
 
 
 
 
Serious Adverse Events 
 Death 
 Re-intervention 
 ALl 
 Major amputation 
 Bypass surgery 
 Hematoma with surgery 
 
 
 
 
 
 
In-Hospital Complications 
 Re-occlusion 
 Renal failure 
 Pseudoaneurysm 
 Bleeding 
 
Other Potential Adverse 
Events 
 Nerve injury 
 AV fistula formation 
 Endarterectomy 
 Infection 
 No long-term adverse effects of peripheral Excimer laser treatment are known at this time. 
 
8.0 ADVERSE DEVICE EVENTS 
 
8.1 
Definition 
An adverse event is any untoward medical occurrence in a clinical investigation 
subject administered the medical device and which does not necessarily have a 
causal relationship with the treatment. An adverse event can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of the device, whether or not 
the event is considered causally related to the use of the device. 
 
Any worsening of a pre-existing condition or illness is considered an adverse event. 
Laboratory abnormalities and changes in vital signs are considered to be adverse 
events only if they result in discontinuation from the study, necessitate therapeutic 
medical intervention, and/or if the investigator considers them to be adverse events. 
 
For adverse events to be considered sporadic or intermittent, the events must be 
similar in nature and severity. 

 
Ra Medical Systems Confidential, RMS-102             Clinical Protocol 05-203-84-10000102 R7                     Page 15 
 
Elective procedures/surgeries that occur during the study will not be considered 
adverse events.  
 
8.2 
Serious Adverse Events  
 
Serious Adverse Device Effect (SADE) 
Adverse device effect that has resulted in any of the consequences characteristic of a serious 
adverse event. 
 
Serious Adverse Event (SAE) 
Adverse event that: 
a) led to a death, 
b) led to a serious deterioration in health that either: 
1) resulted in a life-threatening illness or injury, or 
2) resulted in a permanent impairment of a body structure or a body function, or 
3) required in-patient hospitalization or prolongation of existing hospitalization, or 
4) resulted in medical or surgical intervention to prevent life threatening illness or 
injury or permanent impairment to a body structure or a body function. 
NOTE 1: This includes device deficiencies that might have led to a serious adverse event 
if a) suitable action had not been taken or b) intervention had not been made or c) if 
circumstances had been less fortunate. These are handled under the SAE reporting 
system. 
NOTE 2: A planned hospitalization for pre-existing condition, or a procedure required by 
the Clinical Investigation Plan, without a serious deterioration in health, is not considered 
to be a serious adverse event. 
 
Unanticipated Serious Adverse Device Effect (USADE) 
Serious adverse device effect which by its nature, incidence, severity or outcome has not 
been identified in the current version of the risk analysis report. 
NOTE: Anticipated: an effect which by its nature, incidence, severity or outcome has 
been previously identified in the risk analysis report 
*SADE and SAE definitions adopted from MEDDEV 2.7/3, December 2010, CLINICAL 
INVESTIGATIONS: SERIOUS ADVERSE EVENT REPORTING UNDER DIRECTIVES 
90/385/EEC AND 93/42/EEC.  
 
 
 

 
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9.0 ETHICS 
 
9.1 
Investigator Responsibilities 
The investigator is responsible for ensuring that the clinical study is performed in 
accordance with the protocol, the Declaration of Helsinki, principles of Good Clinical 
Practice (GCP), and applicable regulatory requirements.  
 
9.2 
Institutional Review Board (IRB) 
The investigator will undertake the study after full approval of the protocol and adjunctive 
materials (e.g., informed consent form, advertising) has been obtained from the Internal 
Review Board of the facility and a copy of this approval has been received by the sponsor.   
 
During the conduct of the study, investigators must submit progress reports to the IRB as 
required and request re-review and approval of the study at least once a year. After the 
study is concluded, the investigator should notify the IRB of this status and prepare a final 
report for IRB review. 
 
9.3 
Non-Compliance 
Departures from the protocol and applicable regulatory requirements should be documented 
on the non-compliance log. Subject non-compliance, which is not the control of the 
Investigator and is a subject right, does not need to be reported on the log. Non-compliance 
issues include, but are not limited to, informed consent not obtained, inclusion or exclusion 
criteria not met, missed visits due to site oversight, protocol visits conducted outside the 
defined time period, required testing not completed. 
 
In an emergency, the investigator shall notify the sponsor and the IRB (as required by the 
facility regulations) of any deviations from the investigational plan to protect the life or 
physical well-being of a subject in an emergency. Such notice shall be given as soon as 
possible, but in no event later than 5 working days after the emergency has occurred. 
 
10.0 DEVICE ACCOUNTABILITY 
 
It is the responsibility of the investigator to ensure that all study devices received at the site 
will be accounted for throughout the clinical investigation. The monitor will check device 
accountability during monitoring visits. Unless otherwise instructed by the sponsor, the 
investigator agrees to return all study devices to the sponsor. 
 
11.0 MONITORING RESPONSIBILITIES 
 
Ra Medical Systems, Inc. will serve as the sponsor of this clinical investigation. It is the 
responsibility of Ra Medical as the sponsor of the study to ensure proper monitoring of the 
investigation and to see that all the clinical requirements are met. 
 
The procedural success determination is crossing the lesion that could not be crossed with a 
standard guide wire, and therefore not subject to bias. The procedural success is determined 
using fluoroscopic angiography and is not subject to bias, interpretation, or quantification, 

 
Ra Medical Systems Confidential, RMS-102             Clinical Protocol 05-203-84-10000102 R7                     Page 17 
because the lesion is either crossed or not crossed. Because of these facts, third party 
involvement in determining procedural success would have no added value and provide no 
additional verification. The placebo effect also need not be considered. It is not possible for 
the patient to affect the blockage during the procedure. 
 
All information and data sent to Ra Medical concerning subjects and their participation in 
this investigation will be considered confidential. Only authorized Ra Medical personnel, 
Ra Medical representatives, and regulatory agencies will have access to these confidential 
files. All data used in the analyses and reporting of this investigation will be coded without 
identifiable reference to the subject. 
 
11.1 
Source Documentation 
Source documents are original records, or certified copies of original records, that contain 
clinical findings, observations or other activities in a clinical trial (e.g., hospital records, 
clinical and office charts, laboratory notes, subject diaries, or evaluation checklists) 
necessary for the reconstruction and evaluation of the clinical trial.   
 
Source document worksheets may be used to supplement other medical records, but should 
not be reviewed as the only source. Worksheets must be treated as medical records, that is, 
signed and dated by the person performing the evaluation. 
 
Photocopies of source documents are acceptable for review only if the original document 
can be provided upon request. 
 
The monitor will check the case report form (CRF) data points against the source document 
data points during a monitoring visit. 
 
11.2 
Monitors 
Field and monitoring personnel contact information is as follows: 
Ra Medical Systems, Inc. 
1930 Kellogg Avenue 
   Carlsbad, CA 92008 
Tel: +1-877-635-1800 
Fax: +1-760-804-1657 
 
 
11.3 
Monitoring Visits 
Prior to beginning the study, Ra Medical personnel will contact the investigator to discuss 
the investigational plan and to review the data requirements in detail. 
 
The monitor will visit the investigator during the study to monitor progress, verify that all 
study requirements are completed and answer any questions that may arise. During these 
visits, the monitor may review the subject records to verify that all records and files are 
current and to assure compliance with all requirements of this investigational plan.

 
Ra Medical Systems Confidential, RMS-102             Clinical Protocol 05-203-84-10000102 R7                     Page 18 
 
 
 
 
 
 
 
APPENDIX A 
 
Informed Consent 

 
Ra Medical Systems Confidential, RMS-102             Clinical Protocol 05-203-84-10000102 R7                     Page 19 
Protocol Clinical Protocol 05-203-84-10000102  
RMS-102 
A prospective, multi center pilot study evaluating plaque photoablation using the RA-308 
Excimer Laser in subjects with symptomatic infrainguinal lower extremity vascular disease 
 
 
Patient Informed Consent Form 
1. 
Participant’s Name ___________________________________ 
2. 
Purpose of Project 
You have been invited to participate in a research study sponsored by Ra Medical Systems and Dr. 
_____________. The purpose of this study is to evaluate a device for patients with lower leg 
vascular disease. The device being evaluated in this study is called Ra Medical Systems RA-308 
Excimer Laser System and DABRA Catheter. This device will be used to remove plaque build-
up in your lower leg blood vessels. 
 
You are being asked to volunteer for this study since you are planning to have treatment for 
vascular disease. Since plaque removal is a standard approach for lower leg vascular disease and 
excimer lasers have been commonly used for this procedure, this device is being evaluated in 
patients such as you to evaluate how well it performs. Alternative procedures are amputation, 
bypass surgery, ultrasonic crosser, mechanical crosser, drilling crosser, or rotoblator crosser.   
 
3. 
Description of Research 
The research study to evaluate the RA-308 Excimer Laser and DABRA Catheter is designed to 
evaluate the performance of this device in 50 patients such as you who are scheduled for lower leg 
vascular treatment. In this study, patients who participate will undergo the plaque (material causing 
the blockage) removal from the blood vessels as regularly performed by the surgeon.  However, the 
removal will use the excimer laser. After taking an x-ray of the affected vessels the surgeon will 
insert a catheter or small tube into the groin and then into the leg vessels. The surgeon will advance 
the tubing into the affected area that has the blockage and using the laser he will attempt to clear 
the blockage. The surgeon will then remove the tubing and take another x-ray. Your participation is 
complete at the end of the procedure.  
 
4. 
Risks 
The potential risks associated with participating in this study are those risks which are part of 
vascular surgery treatment and of every surgical procedure. These risks can include infection, 
bleeding, pain, tearing of the vessels, creating a blood clot and other post-surgical complications. 
You may have bruising in your upper leg where the catheter is inserted into your femoral artery, and 
this may be painful. There is also a slight chance of infection where the catheter is inserted. You 
may experience an allergic reaction to the dye, although this is uncommon and is usually very mild. 

 
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Additionally, the fluoroscopy results in a limited level of radiation exposure similar to that of a 
series of X-rays. Your physician will describe these complications to you during your discussion of 
your planned vascular surgery. 
 
5. 
Benefits 
The potential benefit that may be derived from my participation in this study is that your 
vascular blockage will be cleared and blood flow to your legs may be improved.  
6. 
Confidentiality & Voluntary Participation 
You are in my rights to request any clarification and obtain any information regarding this research 
at any time during the course of this study. Furthermore, you are free to withdraw from the study at 
any time that you so desire and if you make that decision it will not affect any future treatment that 
you may require at the facility. 
 
Your medical records and study records may be reviewed by the sponsor of the study, Ra Medical 
Systems, or by regulatory and other governmental agencies. However, the information obtained in 
this study will be held confidential and that at no time will your privacy be violated. 
 
7. 
Compensation 
The facility will be available to provide you with medical or surgical treatment at no cost, in the 
event of damages directly resulting from any of the procedures of the research project. In the event 
of permanent damage, you are entitled to be compensated in accordance with damages suffered. 
 
8. 
Contact Person 
If at any time during the study you have questions regarding the research or your 
participation, you can call your physician, Dr. ____________, Principal Investigator, at 
______________________ (phone number).  You can also contact 
__________________________________________, who represents study participants to the 
Institutional Review Board, a committee whose purpose is to safeguard your rights and 
welfare during the study. 
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. 

 
Ra Medical Systems Confidential, RMS-102             Clinical Protocol 05-203-84-10000102 R7                     Page 21 
CONSENT: 
I have been given an opportunity to ask any questions regarding this research, and my participation, 
and my physician has answered all my questions. By signing this consent form, I understand that I 
have not waived any of my legal rights. I will receive a copy of this consent form, which will show 
all signatures and dates. 
I hereby willingly give my consent to participate in the above-described medical research. 
 
 
 
 
 
 
PATIENT SIGNATURE 
PERSON EXPLAINING THE STUDY 
 
 
 
 
 
PATIENT NAME (PRINT) 
PRINT NAME 
 
ADDRESS: 
 
ADDRESS: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DATE 
DATE 
 
 
I have discussed this research with the patient (and/or his or her legally authorized representative) 
using language which is understandable and appropriate. I believe that I have fully informed this 
patient of the nature of this study, and its benefits and risks, and I believe the patient understood 
this explanation. 
 
 
 
 
 
 
WITNESS 
 
 
 
 
RESEARCHER 
 
 
 
 
 
NAME: 
NAME: 
 
 
 
 
 
DATE 
DATE 
 
 

 
Ra Medical Systems Confidential, RMS-102             Clinical Protocol 05-203-84-10000102 R7                     Page 22 
 
 
APPENDIX B 
 
Case Report Forms 

 
Ra Medical Systems Confidential, RMS-102             Clinical Protocol 05-203-84-10000102 R7                     Page 23 
 
 
 
 
APPENDIX C 
 
Declaration of Helsinki 
 
 
 

 
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WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI 
Ethical Principles for Medical Research Involving Human Subjects 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the 
29th WMA General Assembly, Tokyo, Japan, October 1975 
35th WMA General Assembly, Venice, Italy, October 1983 
41st WMA General Assembly, Hong Kong, September 1989 
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 
and the 52nd WMA General Assembly, Edinburgh, Scotland, October 2000  
Note of Clarification on Paragraph 29 added by the WMA General Assembly, Washington 2002 
Note of Clarification on Paragraph 30 added by the WMA General Assembly, Tokyo 2004 
 
A. 
INTRODUCTION  
1. 
The World Medical Association has developed the Declaration of Helsinki as a statement of 
ethical principles to provide guidance to physicians and other participants in medical 
research involving human subjects. Medical research involving human subjects includes 
research on identifiable human material or identifiable data. 
2. 
It is the duty of the physician to promote and safeguard the health of the people. The 
physician's knowledge and conscience are dedicated to the fulfillment of this duty. 
3. 
The Declaration of Geneva of the World Medical Association binds the physician with the 
words, "The health of my patient will be my first consideration," and the International Code 
of Medical Ethics declares that, "A physician shall act only in the patient's interest when 
providing medical care which might have the effect of weakening the physical and mental 
condition of the patient."  
4. 
Medical progress is based on research which ultimately must rest in part on experimentation 
involving human subjects. 
5. 
In medical research on human subjects, considerations related to the well-being of the 
human subject should take precedence over the interests of science and society. 
6. 
The primary purpose of medical research involving human subjects is to improve 
prophylactic, diagnostic and therapeutic procedures and the understanding of the aetiology 
and pathogenesis of disease. Even the best proven prophylactic, diagnostic, and therapeutic 
methods must continuously be challenged through research for their effectiveness, 
efficiency, accessibility and quality.  
7. 
In current medical practice and in medical research, most prophylactic, diagnostic and 
therapeutic procedures involve risks and burdens.  
8. 
Medical research is subject to ethical standards that promote respect for all human beings 
and protect their health and rights. Some research populations are vulnerable and need 

 
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special protection. The particular needs of the economically and medically disadvantaged 
must be recognized. Special attention is also required for those who cannot give or refuse 
consent for themselves, for those who may be subject to giving consent under duress, for 
those who will not benefit personally from the research and for those for whom the research 
is combined with care.  
9. 
Research Investigators should be aware of the ethical, legal and regulatory requirements for 
research on human subjects in their own countries as well as applicable international 
requirements. No national ethical, legal or regulatory requirement should be allowed to 
reduce or eliminate any of the protections for human subjects set forth in this Declaration. 
B. 
BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH  
10. 
It is the duty of the physician in medical research to protect the life, health, privacy, and 
dignity of the human subject.  
11. 
Medical research involving human subjects must conform to generally accepted scientific 
principles, be based on a thorough knowledge of the scientific literature, other relevant 
sources of information, and on adequate laboratory and, where appropriate, animal 
experimentation. 
12. 
Appropriate caution must be exercised in the conduct of research which may affect the 
environment, and the welfare of animals used for research must be respected. 
13. 
The design and performance of each experimental procedure involving human subjects 
should be clearly formulated in an experimental protocol. This protocol should be submitted 
for consideration, comment, guidance, and where appropriate, approval to a specially 
appointed ethical review committee, which must be independent of the investigator, the 
sponsor or any other kind of undue influence. This independent committee should be in 
conformity with the laws and regulations of the country in which the research experiment is 
performed. The committee has the right to monitor ongoing trials. The researcher has the 
obligation to provide monitoring information to the committee, especially any serious 
adverse events. The researcher should also submit to the committee, for review, information 
regarding funding, sponsors, institutional affiliations, other potential conflicts of interest and 
incentives for subjects.  
14. 
The research protocol should always contain a statement of the ethical considerations 
involved and should indicate that there is compliance with the principles enunciated in this 
Declaration.  
15. 
Medical research involving human subjects should be conducted only by scientifically 
qualified persons and under the supervision of a clinically competent medical person. The 
responsibility for the human subject must always rest with a medically qualified person and 
never rest on the subject of the research, even though the subject has given consent.  
16. 
Every medical research project involving human subjects should be preceded by careful 
assessment of predictable risks and burdens in comparison with foreseeable benefits to the 
subject or to others. This does not preclude the participation of healthy volunteers in 
medical research. The design of all studies should be publicly available. 

 
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17. 
Physicians should abstain from engaging in research projects involving human subjects 
unless they are confident that the risks involved have been adequately assessed and can be 
satisfactorily managed. Physicians should cease any investigation if the risks are found to 
outweigh the potential benefits or if there is conclusive proof of positive and beneficial 
results.  
18. 
Medical research involving human subjects should only be conducted if the importance of 
the objective outweighs the inherent risks and burdens to the subject. This is especially 
important when the human subjects are healthy volunteers.  
19. 
Medical research is only justified if there is a reasonable likelihood that the populations in 
which the research is carried out stand to benefit from the results of the research.  
20. 
The subjects must be volunteers and informed participants in the research project. 
21. 
The right of research subjects to safeguard their integrity must always be respected. Every 
precaution should be taken to respect the privacy of the subject, the confidentiality of the 
patient's information and to minimize the impact of the study on the subject's physical and 
mental integrity and on the personality of the subject. 
22. 
In any research on human beings, each potential subject must be adequately informed of the 
aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations 
of the researcher, the anticipated benefits and potential risks of the study and the discomfort 
it may entail. The subject should be informed of the right to abstain from participation in the 
study or to withdraw consent to participate at any time without reprisal. After ensuring that 
the subject has understood the information, the physician should then obtain the subject's 
freely-given informed consent, preferably in writing. If the consent cannot be obtained in 
writing, the non-written consent must be formally documented and witnessed.  
23. 
When obtaining informed consent for the research project the physician should be 
particularly cautious if the subject is in a dependent relationship with the physician or may 
consent under duress. In that case the informed consent should be obtained by a well-
informed physician who is not engaged in the investigation and who is completely 
independent of this relationship.  
24. 
For a research subject who is legally incompetent, physically or mentally incapable of 
giving consent or is a legally incompetent minor, the investigator must obtain informed 
consent from the legally authorized representative in accordance with applicable law. These 
groups should not be included in research unless the research is necessary to promote the 
health of the population represented and this research cannot instead be performed on 
legally competent persons.  
25. 
When a subject deemed legally incompetent, such as a minor child, is able to give assent to 
decisions about participation in research, the investigator must obtain that assent in addition 
to the consent of the legally authorized representative.  
26. 
Research on individuals from whom it is not possible to obtain consent, including proxy or 
advance consent, should be done only if the physical/mental condition that prevents 
obtaining informed consent is a necessary characteristic of the research population. The 

 
Ra Medical Systems Confidential, RMS-102             Clinical Protocol 05-203-84-10000102 R7                     Page 27 
specific reasons for involving research subjects with a condition that renders them unable to 
give informed consent should be stated in the experimental protocol for consideration and 
approval of the review committee. The protocol should state that consent to remain in the 
research should be obtained as soon as possible from the individual or a legally authorized 
surrogate. 
27. 
Both authors and publishers have ethical obligations. In publication of the results of 
research, the investigators are obliged to preserve the accuracy of the results. Negative as 
well as positive results should be published or otherwise publicly available. Sources of 
funding, institutional affiliations and any possible conflicts of interest should be declared in 
the publication. Reports of experimentation not in accordance with the principles laid down 
in this Declaration should not be accepted for publication.  
C. 
ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH 
MEDICAL CARE 
28. The physician may combine medical research with medical care, only to the extent that the 
research is justified by its potential prophylactic, diagnostic or therapeutic value. When 
medical research is combined with medical care, additional standards apply to protect the 
patients who are research subjects. 
29. The benefits, risks, burdens and effectiveness of a new method should be tested against 
those of the best current prophylactic, diagnostic, and therapeutic methods. This does not 
exclude the use of placebo, or no treatment, in studies where no proven prophylactic, 
diagnostic or therapeutic method exists.  
30. At the conclusion of the study, every patient entered into the study should be assured of 
access to the best proven prophylactic, diagnostic and therapeutic methods identified by the 
study.  
31. The physician should fully inform the patient which aspects of the care are related to the 
research. The refusal of a patient to participate in a study must never interfere with the 
patient-physician relationship. 
32. In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic methods 
do not exist or have been ineffective, the physician, with informed consent from the patient, 
must be free to use unproven or new prophylactic, diagnostic and therapeutic measures, if in 
the physician's judgment it offers hope of saving life, re-establishing health or alleviating 
suffering. Where possible, these measures should be made the object of research, designed 
to evaluate their safety and efficacy. In all cases, new information should be recorded and, 
where appropriate, published. The other relevant guidelines of this Declaration should be 
followed.