Randomised Controlled Trial of Mechanochemical Ablation Versus Cyanoacrylate Adhesive for the Treatment of Varicose Veins
Phase: NA
Conditions: Varicose Veins
Sponsor: Imperial College London

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomised Controlled Trial of Mechanochemical 
Ablation versus Cyanoacrylate Adhesive for the 
Treatment of Varicose Veins 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
 
FULL TITLE 
 
A randomised controlled trial of mechanochemical ablation versus cyanoacrylate 
adhesive for the treatment of varicose veins  
 
SUMMARY 
 
This study will be comparing the treatment of varicose veins using either 
mechanochemical ablation (MOCA) or cyanoacrylate adhesive (CAE). Patients will be 
randomised to receiving either MOCA or CAE. 
 
The pain scores, clinical scores, quality of life scores, occlusion and re-intervention 
rate at 2 weeks, 3, 6 and 12 months as well as the cost effectiveness of each 
intervention will be assessed. 
 
LAY SUMMARY 
 
Varicose vein disease is a common condition affecting the population. Surgery has 
been the main treatment method for a long time, but, for the past decade, minimally 
invasive methods using thermal (heat) technologies were introduced and these were 
found to be more beneficial, especially, as it enables procedures to be carried out 
under local anaesthetic. However, these are often associated with pain especially as 
they use heat and require fluid to be injected around the vein.  
 
More recently, non-thermal methods (no heat method) have been introduced, which 
do not require injection of fluid around the vein. These are potentially better tolerated, 
which could be more advantageous when carrying procedures under local 
anaesthesia. Two of the most common of these non-thermal methods are 
mechanochemical ablation (rotating tip of a catheter wire with simultaneous injection 
of chemical) and cyanoacrylate glue (a chemical which makes the walls of the vein 
stick together). They have been found to have a similar efficacy to the heat methods. 
 
However, there have not been direct comparisons between these non-thermal 
treatment methods and, hence, why this study is being carried out. 
 
The main aim will be to find out which method causes less discomfort. Secondary 
objectives will be to assess the pain level over the ensuing few days, change in quality 
of life, clinical severity score, degree of bruising and inflammation, time to return to 
normal activities/work, re-intervention rates as well as the cost-effectiveness of each 
method. 
 
 
 
 
 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
OBJECTIVES 
 
• 
Primary Objective 
 
Pain score during saphenous vein ablation  
 
• 
Secondary Objective 
 
The secondary objectives would be to compare the two treatment groups with 
respect to: 
o The pain score at the end of the procedure 
o The quality of life scores at baseline, 2 weeks, 3 months, 6 months 
and 12 months using the EQ-5D, AVVQ and CIVIQ scores 
o The clinical change using the VCSS at baseline, 2 weeks, 3 months, 6 
months and 12 months  
o The pain score over the first 10 days 
o The degree of bruising at 2 weeks (based on a clinical examination) 
o The time taken to return to work and normal activities 
o Occlusion rates at 3 months, 6 months and 12 months  
o Re-intervention rate at 12 months 
o Comparison of the cost effectiveness of each intervention  
 
Background 
 
Varicose veins are common and are known to affect approximately one third of the 
population1. Chronic venous disease (CVD) has been shown to have a negative impact 
on the quality of life of patients and treatment of varicose veins has been demonstrated 
to lead to improvement in the quality of life of patients2-4. Over the past decade, new 
endovenous techniques have been introduced and these are felt to be cost-effective, 
especially, when performed in an outpatient or ‘office-based’ setting5. These 
endovenous ablation methods (almost exclusively radiofrequency ablation (RFA) or 
endovenous laser ablation (EVLA) employ mainly thermal energy, to treat varicose 
veins. The American Venous Forum (AVF) and the National Institute of Clinical 
Excellence (NICE) guidelines published in July 2013 recommended the use of 
endovenous thermal ablation techniques, namely radiofrequency ablation (RFA) or 
endovenous later ablation (EVLA), as first line treatment for truncal reflux6-8. Occlusion 
rates of greater than 90% have been demonstrated in studies looking at these two 
methods at up to 2 years of follow-up 9-12.  
 
However, because they make use of thermal energy to denature the venous wall, they 
have the potential of causing pain, skin burns, skin pigmentation, nerve damage and, 
even, arteriovenous fistula formation13, 14. To minimise these possible complications, 
tumescent anaesthesia has to be infiltrated around the vein to be treated. This, in turn, 
can be a source of discomfort to patients. 
 
More recently, newer non-thermal, non-tumescent (NTNT) ablation techniques have 
been introduced in order to reduce these complications. Mechanochemical ablation 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
(MOCA) and cyanoacrylate adhesive injection (CAE) are two examples of these 
NTNTs15, 16. So far, they have been shown to be less painful than the thermal methods, 
but also equivalent to them in terms of quality of life improvement, time to return to 
normal activities and occlusion rates17, 18. This, therefore, indicates that they may one 
day be considered more favourably than endothermal ablation.  
 
NICE has also recently produced interventional procedures guidance for the use of 
both MOCA and CAE. 
 
However, there has not been any direct head-to-head comparison of these two non-
thermal methods. We, therefore, propose to undertake a randomised controlled study 
comparing mechanochemical ablation and cyanoacrylate adhesive in the treatment of 
varicose veins. 
 
Description 
 
This will be a randomised clinical trial comparing MOCA to CAE. Patients will be 
randomised into group A (MOCA) or group B (CAE). Only the endovenous ablation 
part of the procedure will be randomised while the decision as to whether patients 
should receive treatment of their varicose tributaries will be at the discretion of the 
clinical team. 
 
The device used for MOCA (group A) will be the ClariVein® mechanochemical 
ablation (MOCA) device (Vascular Insights, Madison, CT, USA). 
 
The device used for CAE (group B) will be the VenaSealTM Closure System 
(Medtronic, Minneapolis, Minnesota, USA). 
 
Re-intervention of the treated saphenous veins will not be decided until at least 3 
months after their initial procedure. 
 
Target Population 
 
Patients referred for treatment of symptomatic varicose veins will be recruited if they 
are found to have primary great saphenous (GSV) or short saphenous vein (SSV) 
incompetence on colour duplex scan. Patients will be identified at their clinic 
appointment and provided with further information regarding the study. 
 
Inclusion Criteria 
 
• 
Adults over 18 years of age 
• 
Symptomatic GSV or SSV vein reflux > 0.5 seconds on colour Duplex 
 
 
Exclusion Criteria  
 
• 
Current DVT 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
• 
Recurrent varicose veins 
• 
Arterial disease (ABPI<0.8) 
• 
Vein diameter < 3mm 
• 
Patient who are unwilling to participate 
• 
Inability or unwillingness to complete questionnaires  
• 
Adverse reaction to sclerosant or cyanoacrylate 
• 
Not been involved in another venous trial for at least 6 months  
 
Intervention 
 
On the day of their procedures, patients will be asked to sign a study consent form for 
inclusion into the study. They will then be allocated a study number. 
 
Patients will be randomised to have MOCA (group A) or CAE (group B) to treat their 
saphenous veins. 
 
Randomisation will be carried out using an internet-based randomisation service 
(Sealed Envelope). 
 
At baseline, basic demographic data will be collected from each patient (age, sex, 
height, weight, number of children, occupation, etc.; see Appendix 1). Patients will also 
be asked to provide their contact details (address, postcode, emails or telephone 
numbers) to enable correspondence for follow-up appointments. 
 
Patients will be asked to fill quality of life questionnaires (EQ-5D, AVVQ and CIVIQ) 
and will have their clinical scores assessed (CEAP and VCSS).  
 
The primary outcome measure will be to record the pain score immediately following 
completion of the endovenous ablation using a 100mm visual analogue scale (VAS) 
and a 0-10 number scale.  
 
Once the pain score has been recorded, concurrent phlebectomy or foam 
sclerotherapy will then be carried out, if deemed necessary by the clinical team. At the 
end of this part of the procedure, the pain score will again be assessed, using the VAS 
and number scale. 
 
Patients would be allowed to leave once they have spent a complication free period in 
the department. On discharge, all patients will be provided with compression stockings 
to wear for 4 days. They will also be provided with a diary to record their post-
procedural pain every day for the first 10 post-operative days using a validated 100mm 
visual analogue scale (VAS) as well as to record when they return to their normal 
activities and are back to work.  
 
Patients will also be asked to attend a follow-up for research purposes at 2 weeks, 3 
months, 6 and 12 months.  
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
Patients’ GP will also be sent a letter to inform them of their patient’s participation in 
the study. 
 
Risks of Procedures 
 
Complications are possible following the varicose vein interventions and they are 
listed below. “Low risk” indicates that the risk of the complication happening is less 
than 1% and “moderate risk” indicates that the risk of the complication occurring is 
between 1-5%. 
 
The possible complications usually associated with the MOCA technique include: 
• 
Bleeding (low risk) 
• 
Infection (low risk) 
• 
Thrombophlebitis (moderate risk) 
• 
Venous thromboembolism (low risk) 
• 
Skin discolouration (low risk) 
• 
Rotating wire getting caught (low risk) 
 
The possible complications usually associated with the CAE method include: 
• 
Bleeding (low risk) 
• 
Infection (low risk) 
• 
Thrombophlebitis (moderate risk) 
• 
Venous thromboembolism (low risk) 
• 
Skin discolouration (low risk) 
 
Follow-up 
 
For research purposes, patients will be asked to attend a follow-up appointment in 
the outpatient clinic at 2 weeks, 3 months, 6 and 12 months. 
 
Follow-up at 2 Weeks 
At the 2 weeks’ follow-up, the diary containing details of the pain scores and how soon 
patients were able to return to normal activities/work will be collected. In addition, 
patients will be asked and examined for any bruising or phlebitis they have had after 
their procedure. They will undergo a clinical examination and the Venous Clinical 
Severity Score (VCSS) will be recorded and will be asked to fill in the EQ-5D, AVVQ 
and CIVIQ scores. No decision regarding re-treatment will be taken at this point. No 
risks are expected at this follow-up. 
 
Follow-up at 3 Months, 6 Months and 12 Months 
At the 3 months, 6 months and 12 months follow-up, patients will undergo another 
clinical examination and their VCSS will be recorded. They will also be asked to fill the 
EQ-5D, AVVQ and the CIVIQ scores. They will have a venous Duplex scan to 
determine occlusion of the treated vein.  This will involve measurement of the vein with 
anonymised images for analysis. 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
As from the third month, patients found to have recurrence of their truncal veins will be 
assessed to see if they are symptomatic and require re-intervention. The method used 
for re-intervention will be dependent on the choice of the consultant in charge of the 
patient. No risks are expected to happen at follow-up, although patients with 
recurrence face possible complications based on the re-intervention procedures they 
will undergo. 
Sample Size and Study Duration 
 
We estimated the sample size needed to observe a mean difference of at least 10mm 
(standard deviation: 20mm) between the two interventions. With power set at 80% and 
5% significance equivalence, we would need to recruit 128 patients (64 patients per 
group).  
 
If a drop-out rate from follow-up of 30% is estimated, the total number to recruit is 183. 
If we recruit at least 3 patients per week, this will be approximately a total of 156 
patients that could potentially be randomised over the year and 180 patients over 60 
weeks (approximately 14 months). Thus, with 12 months follow-up the study will be 
running for 26 months with a target recruitment of 180 patients.  
 
Settings 
 
This study will be conducted at the Charing Cross Hospital (Imperial College London, 
UK) as well as the Singapore General Hospital and the Sengkang General Hospital 
(Singapore). 
 
 
 
 
Funding 
 
This study is currently not receiving any funding, but it is anticipated that application 
will be made for external funding during the course of the clinical trial. 
 
 
ETHICAL ARRANGEMENTS 
 
Ethical approval will be sought from a Regional Research Ethics Committee as per the 
National Research Ethics Service (NRES) and Health Research Authority (HRA). 
Patients will be screened by Roshan Bootun (or another research fellow), who is also 
a member of the direct care team, and patients thought eligible will be provided with 
information material about the trial and varicose veins and its treatments.  
 
They will be invited to attend for their varicose vein procedures another day and will 
have until then to consider their participation into the trial (more than 24 hours to 
consider).  
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
On the day of their procedure, they will be asked by Roshan Bootun (or another 
research fellow/nurse) to confirm their consent by providing a written consent prior to 
participating in the trial.  
 
 
DATA HANDLING & DISSEMINATION OF RESULTS 
All patient data will be anonymised and stored on a password protected database 
under the guidelines of the Data Protection Act 1998. Patient records will be kept on 
paper in the form of the diary card questionnaires and clinical scoring sheets. These 
will be kept in a locked filling cabinet at the and stored at the Charing Cross Hospital 
for 10 years in accordance with the Imperial College Trust Policy. 
 
Data and study findings will be presented locally within the hospital, as well as national 
and international peer reviewed presentations and peer-reviewed journals. 
Criteria for Electively Stopping the Trial or Other Research Prematurely  
The trial may be stopped prematurely due to loss of equipoise or any major adverse 
effect as a result of treatment in any of the treatment arms. 
Adverse events 
No significant adverse events are expected. 
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study 
subject. 
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or 
effect that: 
·         Results in death 
·         Is life-threatening – refers to an event in which the subject was at risk of death 
at the time of the event; it does not refer to an event which hypothetically might have 
caused death if it were more severe 
·         Requires hospitalisation, or prolongation of existing inpatients’ 
hospitalisation 
·         Results in persistent or significant disability or incapacity 
·         Is a congenital anomaly or birth defect 
 
REPORTING PROCEDURES 
All adverse events should be reported. 
Depending on the nature of the event the reporting procedures below should be 
followed. 
Any questions concerning adverse event reporting should be directed to the Chief 
Investigator in the first instance.  
 
Adverse Events (AE) 
All such events, whether expected or not, should be recorded.  
  
Serious Adverse Events (SAE) 
An SAE form should be completed and faxed to the Chief Investigator within 24 hours.   
 All SAEs should be reported to the Research Ethical Committee where in the opinion 
of the Chief Investigator, the event was: 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
·         ‘related’, ie resulted from the administration of any of the research procedures; 
and 
·         ‘unexpected’, ie an event that is not listed in the protocol as an expected 
occurrence 
  
Reports of related and unexpected SAEs should be submitted within 15 days of the 
Chief Investigator becoming aware of the event, using the NRES SAE form for non-
IMP studies.  
 
Local investigators should report any SAEs as required by their Local Research Ethics 
Committee, Sponsor and/or Research & Development Office. 
 
In the event of any harm to participants in the trial, Imperial College holds Public 
Liability (“negligent harm”) and Clinical Trial (“non-negligent harm”) insurance policies 
which apply to this trial. 
ETHICS APPROVAL 
 
The Chief Investigator has obtained approval from the xxx Research Ethics Committee 
and the HRA.  The study must be submitted for Site Specific Assessment (SSA) at 
each participating NHS Trust. The Chief Investigator will require a copy of the Trust 
R&D approval letter before accepting participants into the study.  The study will be 
conducted in accordance with the recommendations for physicians involved in 
research on human subjects adopted by the 18th World Medical Assembly, Helsinki 
1964 and later revisions. 
 
CONSENT  
 
Consent to enter the study will be sought from each participant only after a full 
explanation has been given, an information leaflet offered and time allowed for 
consideration. Signed participant consent will be obtained. The right of the participant 
to refuse to participate without giving reasons will be respected. After the participant 
has entered the study the clinician remains free to give alternative treatment to that 
specified in the protocol at any stage if he/she feels it is in the participant’s best interest, 
but the reasons for doing so will be recorded. In these cases the participants remain 
within the study for the purposes of follow-up and data analysis. All participants are 
free to withdraw at any time from the protocol treatment without giving reasons and 
without prejudicing further treatment. 
 
CONFIDENTIALITY 
 
The Chief Investigator will preserve the confidentiality of participants taking part in the 
study and is registered under the Data Protection Act. 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
Patient details will be anonymised as each participant will be allocated a study number. 
The allocated study number key code will be kept on a password protected NHS 
computer at all sites. 
 
Patient details, including contact information (address, email, telephone numbers etc.), 
will be recorded on paper form. This paper form will be kept in a locked filing cabinet 
in a locked Vascular Research Office, located in the Section of Vascular Surgery on 
Floor 4 North at Charing Cross Hospital (university office). The contact details will be 
discarded once patients have been advised of the findings of the study (approximately, 
within 6-12 months following completion of the study). 
 
All anonymised patient details with the allocated study number used as identifier will 
be stored electronically on a password protected access database on an Imperial 
College London university computer. 
 
INDEMNITY 
 
Imperial College London holds negligent harm and non-negligent harm insurance 
policies which apply to this study. 
 
SPONSOR 
 
Imperial College London will act as the main Sponsor for this study. Delegated 
responsibilities will be assigned to the NHS trusts taking part in this study.   
 
FUNDING 
 
There are currently no funders for this study. However, external funding may be 
sought in the future. 
 
 
AUDITS  
 
The study may be subject to inspection and audit by Imperial College London under 
their remit as sponsor and other regulatory bodies to ensure adherence to GCP and 
the NHS Research Governance Framework for Health and Social Care (2nd edition).  
 
Reference: 
 
1. 
Evans CJ, Fowkes FG, Ruckley CV and Lee AJ. Prevalence of varicose veins 
and chronic venous insufficiency in men and women in the general population: 
Edinburgh Vein Study. Journal of epidemiology and community health. 1999; 53: 
149-53. 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
2. 
Smith JJ, Garratt AM, Guest M, Greenhalgh RM and Davies AH. Evaluating 
and improving health-related quality of life in patients with varicose veins. J Vasc 
Surg. 1999; 30: 710-9. 
3. 
MacKenzie RK, Paisley A, Allan PL, Lee AJ, Ruckley CV and Bradbury AW. 
The effect of long saphenous vein stripping on quality of life. J Vasc Surg. 2002; 35: 
1197-203. 
4. 
Biemans AA, Kockaert M, Akkersdijk GP, et al. Comparing endovenous laser 
ablation, foam sclerotherapy, and conventional surgery for great saphenous varicose 
veins. J Vasc Surg. 2013; 58: 727-34.e1. 
5. 
van den Bos R, Arends L, Kockaert M, Neumann M and Nijsten T. 
Endovenous therapies of lower extremity varicosities: a meta-analysis. J Vasc Surg. 
2009; 49: 230-9. 
6. 
Gloviczki P and Gloviczki ML. Guidelines for the management of varicose 
veins. Phlebology / Venous Forum of the Royal Society of Medicine. 2012; 27 Suppl 
1: 2-9. 
7. 
Marsden G, Perry M, Kelley K and Davies AH. Diagnosis and management of 
varicose veins in the legs: summary of NICE guidance. BMJ (Clinical research ed). 
2013; 347: f4279. 
8. 
National Institute for Health and Care Excellence. NICE Clinical Guideline 
Centre. Varicose veins in the legs - the diagnosis and management of varicose veins 
(Clinical guideline 168). NICE, 2013. 
9. 
Subramonia S and Lees T. Randomized clinical trial of radiofrequency 
ablation or conventional high ligation and stripping for great saphenous varicose 
veins. The British Journal of Surgery. 2010; 97: 328-36. 
10. 
Rasmussen LH, Lawaetz M, Bjoern L, Vennits B, Blemings A and Eklof B. 
Randomized clinical trial comparing endovenous laser ablation, radiofrequency 
ablation, foam sclerotherapy and surgical stripping for great saphenous varicose 
veins. The British Journal of Surgery. 2011; 98: 1079-87. 
11. 
Tolva VS, Cireni LV, Bianchi PG, Lombardo A, Keller GC and Casana RM. 
Radiofrequency ablation of the great saphenous vein with the ClosureFAST 
procedure: mid-term experience on 400 patients from a single centre. Surgery today. 
2013; 43: 741-4. 
12. 
Goode SD, Chowdhury A, Crockett M, et al. Laser and radiofrequency 
ablation study (LARA study): A randomised study comparing radiofrequency ablation 
and endovenous laser ablation (810 nm). European Journal of Vascular and 
Endovascular Surgery. 2010; 40: 246-53. 
13. 
Anwar MA, Lane TR, Davies AH and Franklin IJ. Complications of 
radiofrequency ablation of varicose veins. Phlebology / Venous Forum of the Royal 
Society of Medicine. 2012; 27 Suppl 1: 34-9. 
14. 
Dexter D, Kabnick L, Berland T, et al. Complications of endovenous lasers. 
Phlebology / Venous Forum of the Royal Society of Medicine. 2012; 27: 40-5. 
15. 
Elias S and Raines JK. Mechanochemical tumescentless endovenous 
ablation: final results of the initial clinical trial. Phlebology / Venous Forum of the 
Royal Society of Medicine. 2012; 27: 67-72. 
16. 
Almeida JI, Javier JJ, Mackay E, Bautista C and Proebstle TM. First human 
use of cyanoacrylate adhesive for treatment of saphenous vein incompetence. 
Journal of Vascular Surgery: Venous and Lymphatic Disorders. 2013; 1: 174-80. 
17. 
Morrison N, Gibson K, McEnroe S, et al. Randomized trial comparing 
cyanoacrylate embolization and radiofrequency ablation for incompetent great 
saphenous veins (VeClose). J Vasc Surg. 2015; 61: 985-94. 
18. 
Lane T, Bootun R, Dharmarajah B, et al. A multi-centre randomised controlled 
trial comparing radiofrequency and mechanical occlusion chemically assisted 
ablation of varicose veins - Final results of the Venefit versus Clarivein for varicose 
veins trial. Phlebology / Venous Forum of the Royal Society of Medicine. 2016. 
  

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
 
APPENDIX 1: Quality of Life Questionnaire 
 
Hospital Number---------------------------  
 
MALE  
FEMALE 
 
 
 
 
 
 
 
 
Date of birth--------------------------------- 
 
 
 
 
 
 
 
Age ----------------------------------------- 
 
Occupation---------------------------------- 
 
 
 
 
Date------------------------------------------  
 
Past Medical History 
 
 
 
 
Yes  
No 
 
 
 
 
Yes  
No
 
 
Bleeding disorder 
 
 
  
 
IHD 
 
 
 
 
DVT/PE 
 
 
 
 
  
 
Leg ulcers 
 

 
 
Diabetes 
 
 
 
 
 
Hypertension  
 
 
 
Medications 
----------------------------------------------------------------------------------------------------------------------
-------------------------------- 
 
Previous treatment to Varicose Veins 
 
Side 
Site 
Date 
Treatment type 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 2: Pre Operative Clinical Assessment 
Score 
Definition 
0 
Asymptomatic 
1 
Symptomatic, but able to carry out usual activities with out 
compressive therapy 
2 
Able to carry out usual activities only with compressive therapy and/or 
limb elevation 
3 
Unable to carry out usual activities even with compression and/or 
elevation 
 
Usual activities = patients activities before the onset of disability due 
to venous disease 
 
 
 
 
 
 
 
 
 
Number of 
Pregnancies 
 
Weight/ Kg 
 
BMI>30 
Yes 
No 
OCP or HRT 
Yes 
No 
Smoker 
Yes 
No 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
Appendix 3: Venous Clinical Severity Score (VCSS) 
 Please indicate right or left leg or bilateral (R, L or B) 
 
Absent 
Mild 
Moderate 
Severe 
Pain 
None 
Occasional, 
non/ no 
analgesia 
restricting 
With 
moderate 
activity, 
occasional 
analgesia 
Daily, severe 
limitations, 
regular analgesia 
Varicose 
veins>4mm 
None 
Few 
Multiple GSV 
Extensive GSV 
and LSV 
Venous 
oedema 
None 
Evening/ankle 
Afternoon/ 
above knee 
Morning/requiring 
elevation 
Skin 
pigmentation 
None 
Limited and 
old/brown 
Diffuse lower 
third/ purple 
 
Wide/ purple 
 
Inflammation 
None 
Mild cellulitis in 
marginal area 
Moderate 
involving 
most of gaiter 
area  
Severe cellulitis 
or significant 
eczema 
Induration 
None 
 Focal <5cm 
Medial or 
lateral less 
than lower 
1/3 
1/3 of lower leg 
or more 
Number of 
active ulcers 
0 
1 
 
 
2 
 
 
3 
 
 
Active ulcer 
duration 
None 
<3 months 
>3 months  
<12 months 
>12 months 
Active ulcer 
diameter( cm) 
None 
<2 
2-6 
>6 
Compression 
Not used or 
non 
compliant 
Intermittent use 
Stockings 
worn most 
days 
Stockings worn 
daily 
 
Total 
 
 
 
 
 
 
Appendix 4: Clinical-Etiology-Anatomy-Pathophysiology (CEAP Classification) 
Clinical 
 
0 
1A 
1S 
2A 
2S 
3A 
3S 
4aA 
4aS 
4bA 
4bS 
5A 
5S 
6 
Etiology 
 
Congenital 
Primary 
Secondary 
No venous cause identified 
Anatomy 
 
Superficial 
Deep 
Perforating 
No venous location identified 
Pathology 
 
Reflux 
Obstruction 
Both 
No venous pathology identified 
Class 0 No visible or palpable veins 
Class 1 Telangiectasia, reticular veins  
 
Class 5 Skin changes and healed 
ulceration 
Class 2 Varicose Veins 
 
 
Class 6 Active venous ulcers 
Class 3 Oedema without skin changes 
Class 4 Skin changes ascribed to venous disease 
 
A= Asymptomatic 
 
4a) Pigmentation or eczema 
 
 
S= Symptomatic 
 
4b) Lipodermatoscerosis or atrophie blanche  
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
Appendix 5. Quality of Life Questionnaires 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
 
 
 
 
 
 
 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
Appendix 6: Aberdeen Varicose Vein Questionnaire 
 
 
 
1. 
Please draw in your varicose veins in the diagram(s) 
below:- 
 
 
      Legs viewed 
 
 
 
 
 
       Legs viewed 
 
        from front 
 
 
 
 
 
         from back 
 
2. 
In the last two weeks, for how many days did your 
varicose veins cause you pain or ache? 
(Please tick one box for each leg) 
R Leg 
L Leg 
None at all 
 
 
 
Between 1 and 5 days 
 
 
 
Between 6 and 10 days 
 
 
 
For more than 10 days 
 
 
 
 
3. 
During the last two weeks, on how many days did you take 
painkilling tablets for your varicose veins? 
(Please tick one box for each leg) 
R Leg 
L Leg 
None at all 
 
 
 
Between 1 and 5 days 
 
 
 
Between 6 and 10 days 
 
 
 
For more than 10 days 
 
 
 
 
 
 
 
YOUR VARICOSE VEINS 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
4. 
In the last two weeks, how much ankle swelling have you 
had? 
 
(Please tick one box)                                                            None at all  
 
Slight ankle swelling 
 
 
Moderate ankle swelling (eg. causing you 
to sit with your feet up whenever possible) 
 
  
Severe ankle swelling  (eg. causing you 
 difficulty putting on your shoes) 
 
       
5. 
In the last two weeks, have you worn support stockings or 
tights? 
 (Please tick one box for each leg) 
R Leg 
L Leg 
No 
 
 
 
 
Yes, those I bought myself without 
a doctor's prescription 
 
 
 
 
Yes, those my doctor prescribed for 
me which I wear occasionally 
 
 
 
 
Yes, those my doctor prescribed for 
me which I wear every day 
 
 
 
 
6. 
In the last two weeks, have you had any itching in 
association with your varicose veins? 
 (Please tick one box for each leg) 
R Leg 
L Leg 
No 
 
 
 
Yes, but only above the knee 
 
 
 
Yes, but only below the knee 
 
 
 
Both above and below the knee 
 
 
 
 
7. 
Do you have purple discolouration caused by tiny blood 
vessels in the skin, in association with your varicose 
veins? 
(Please tick one box for each leg) 
R Leg 
L Leg 
No 
 
 
 
Yes 
 
 
 
 
8. 
Do you have a rash or eczema in the area of your ankle? 
(Please tick one box for each leg) 
R Leg 
L Leg 
No 
 
 
 
 
Yes, but it does not require any treatment  
from a doctor or district nurse 
 
 
 
 
Yes, and it requires treatment from  
my doctor or district nurse 
 
 
 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
9. 
Do you have a skin ulcer associated with your varicose 
veins? 
(Please tick one box for each leg) 
R Leg 
L Leg 
No 
 
 
 
Yes 
 
 
 
 
10. 
Does the appearance of your varicose veins cause you 
concern? 
(Please tick one box)                                                                        No 
 
 
Yes, their appearance causes 
me slight concern 
 
 
Yes, their appearance causes  
me moderate concern 
 
  
Yes, their appearance causes  
me a great deal of concern 
 
  
11. 
Does the appearance of your varicose veins influence 
your choice of clothing including tights? 
           (Please tick one box)                                                                         No 
 
Occasionally 
 
Often 
 
Always 
 
 
12. 
During the last two weeks, have your varicose veins 
interfered with your work/ housework or other daily 
activities? 
  (Please tick one box)                                                                          No 
 
 
I have been able to work but my work  
has suffered to a slight extent 
 
 
 I have been able to work but my work  
has suffered to a moderate extent 
 
 
My veins have prevented me from  
working one day or more 
 
 
13. 
During the last two weeks, have your varicose veins 
interfered with your leisure activities (including sport, 
hobbies and social life)? 
(Please tick one box)                                                                          No 
 
 
Yes, my enjoyment has suffered  
to a slight extent 
 
 
Yes, my enjoyment has suffered 
to a moderate extent 
 
 
Yes, my veins have prevented me taking  
part in any leisure activities 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
 
Appendix 7 
C I V I Q-14 
SELF-QUESTIONNAIRE PATIENTS 
In English language for UK 
 
 
Many people complain of leg pain. We would like to find out how often these 
leg problems occur and to what extent they affect the everyday lives of those 
who suffer from them. 
 
Below you will find a list of symptoms, sensations or types of discomfort that 
you may be experiencing and which may make everyday life hard to bear to a 
greater or lesser extent. For each symptom, sensation, or type of 
discomfort listed, we would like you to answer in the following way: 
 
Please indicate if you have experienced what is described in each sentence, 
and if the answer is ‘yes’, how intense it was. There are five possible answers, 
and we would like you to circle the one which best describes your situation. 
 
 
 
Circle 1 
if you feel the symtom, sensation of discomfort 
described does not apply to you 
 
Circle 2, 3, 4 or 5 
 
if you have felt it to a greater or lesser extent 
 
 
 
 
 
 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
QUALITY OF LIFE WITH VENOUS INSUFFICIENCY 
 
 
1)  During the past four weeks, have you had any pain in your ankles or legs, and how 
severe has this pain been? 
Circle the number that applies to you. 
 
No  
pain 
Slight  
pain 
Moderate 
pain 
Considerable 
pain 
Severe 
pain 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
 
 
2)  During the past four weeks, how much trouble have you experienced at work or 
during your usual daily activities because of your leg problems? 
Circle the number that applies to you. 
 
No trouble 
Slight trouble 
Moderate trouble 
Considerable 
trouble 
Severe trouble 
 
 
 
 
 
1 
2 
3 
4 
5 
 
 
 
 
3)  During the past four weeks, have you slept badly because of your leg problems, and 
how often? 
Circle the number that applies to you. 
 
Never 
Rarely 
Fairly 
often 
Very  
often 
Every 
night 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
 
 
 
 
During the past four weeks, how much trouble have you experienced 
carrying out the actions and activities listed below because of 
your leg problems? 
For each statement in the table below, indicate how much trouble you 
have experiened by circling the number chosen. 
 
 
No trouble 
Slight trouble 
Moderate 
trouble 
Considerable 
trouble 
Could not  
do it 
4)  Climbing several 
flights of stairs 
1 
2 
3 
4 
5 
5)  Crouching, 
Kneeling down 
1 
2 
3 
4 
5 
6)  Walking at a 
brisk pace 
1 
2 
3 
4 
5 
7)  Going out for 
the evening, going 
to a wedding, a 
party, a cocktail 
party… 
1 
2 
3 
4 
5 
8)  Playing a sport, 
exerting yourself 
physically 
1 
2 
3 
4 
5 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
  
Leg problems can also affect your mood. How closely do the following 
statements correspond to what you have felt during the past four 
weeks? 
 
For each statement in the table below, circle the number that applies 
to you. 
 
 
 
Not at all 
 
A little 
 
 
Moderately 
 
A lot 
 
Completely  
 
9)  I have felt 
nervous/tense 
1 
2 
3 
4 
5 
10)  I have felt I 
am a burden 
1 
2 
3 
4 
5 
11)  I have felt 
embarrassed about 
showing my legs 
1 
2 
3 
4 
5 
12)  I have become 
irritated easily 
1 
2 
3 
4 
5 
13)  I have felt as if 
I am handicapped 
1 
2 
3 
4 
5 
14)  I have not felt 
like going out 
1 
2 
3 
4 
5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
Appendix 8. Procedural Pain Score 
Date:………………………….  
 
Hosp. No.:-………………….. 
 
This is to assess the amount and duration of pain you experience during this treatment. 
 
Please put a mark on the line to indicate the maximum pain score you experience as 
well as a number between 0-10 to indicate the pain score over 10 (10 = worst pain 
imaginable). 
Also, please indicate the duration of the discomfort. 
 
Example: If your pain score is roughly about 3 over 10 (10 being the worst pain imaginable), 
you might want to indicate it as below: 
 
Discomfort 
No 
pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
 
 
 
 
 
Post-Endovenous Ablation 
 
 
Maximum Discomfort 
 
 
Maximum 
Discomfort 
No 
pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
 
 
 
 
 
Please Tick 
Maximum discomfort lasted a few seconds 
 
Maximum discomfort lasted a few minutes 
 
Maximum discomfort lasted longer than a few minutes 
 
 
 
Average Discomfort 
 
 
Average 
Discomfort 
No 
pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
 
 
 
 
 
Please Tick 
Maximum discomfort lasted a few seconds 
 
Maximum discomfort lasted a few minutes 
 
Maximum discomfort lasted longer than a few minutes 
 
 
 
 
 
| 
3 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
 
Post-tributary Treatment 
 
 
Maximum Discomfort 
 
 
Maximum 
Discomfort 
No 
pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
 
 
 
 
 
Please Tick 
Maximum discomfort lasted a few seconds 
 
Maximum discomfort lasted a few minutes 
 
Maximum discomfort lasted longer than a few minutes 
 
 
 
Average Discomfort 
 
 
Average 
Discomfort 
No 
pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
 
 
 
 
 
Please Tick 
Maximum discomfort lasted a few seconds 
 
Maximum discomfort lasted a few minutes 
 
Maximum discomfort lasted longer than a few minutes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 9. Patient Diary 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
 
Please indicate at what stage you were able to return to work and your normal daily 
activities (the activities you were able to do prior to treatment).  
 
Please also indicate the day when you stopped wearing the compression stockings (if 
provided). 
 
(Please tick one box) 
 
 
Day I was able to 
resume my normal 
activities 
Day I returned to 
work  
Day I stopped wearing 
compression 
stockings 
Day of surgery 
 
 
 
Day after surgery 
 
 
 
2 days after surgery 
 
 
 
3 days after surgery 
 
 
 
4 days after surgery 
 
 
 
5 days after surgery 
 
 
 
6 days after surgery 
 
 
 
7 days after surgery 
 
 
 
8 days after surgery 
 
 
 
9 days after surgery 
 
 
 
10 days after surgery 
 
 
 
>10 days after 
surgery 
 
 
 
 
 
 
 
 
Please return to: 
Professor Alun Davies 
Academic Department of Vascular Surgery  
Floor 4 East 
Charing Cross Hospital 
Fulham Palace Road 
London 
W6 8RF 
Tel.: 02033117320 
 
 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
Appendix 10. Patient Pain Diary (VAS) 
Please put a mark on the line to indicate your maximum pain score on each day. 
Please also write a score from 0 to 10 for your maximum pain on each day. 
Example: If your pain score on day 4 is roughly about 5 over 10 (10 being the worst pain 
imaginable), you might want to indicate it as below: 
Day 4 
No pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
 
 
Study Diary: 
(0 = no pain and 10 = worst pain imaginable) 
Day 0 
No pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
Day 1 
No pain 
 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
Day 2 
No pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
Day 3 
No pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
Day 4 
No pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
Day 5 
No pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
Day 6 
No pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
Day 7 
No pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
Day 8 
No pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0  
 
10 
 
Day 9 
No pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0 
 
 
10 
 
Day 10 
No pain 
 
 
 
 
Worst pain 
imaginable 
 
 
0 
 
 
10 
 
Appendix 11. Ecchymosis Score 
 
| 
5 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
Patient No.:………………………………. 
 
Date:………………………………………… 
 
 
Ecchymosis at 2 weeks 
Grade 
Treated Area with Ecchymosis (%) 
 
0 
None 
 
1 
<25 
 
2 
25-50 
 
3 
50-75 
 
4 
75-100 
 
5 
Extension above or below treated segment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
IRAS Project ID: 227777  
ClinicalTrial.gov registration number: NCT03392753 
RCT of Mechanochemical Ablation versus Cyanoacrylate Adhesive v5.0 (21 November  2018)  
Symptomatic patients with varicose vein reflux > 
0.5 seconds on venous Duplex 
Appendix 12. Trial Flowchart 
 
Patients undergo endovenous ablation  
2 weeks: diary returned and follow-up in clinic 
with VCSS, AVVQ, CIVIQ and EQ-5D  
Patients discharged home with diary to fill 
(recording pain scores, time to return to normal 
activities/work, complications and compliance) 
Consenting patients complete VCSS, AVVQ, 
CIVIQ and EQ-5D 
Randomisation 
Group B - Cyanoacrylate 
Group A – Mechanochemical Ablation 
6 months: follow-up in clinic with VCSS, AVVQ, 
CIVIQ and EQ-5D as well as venous Duplex  
Analysis of results and cost evaluation 
 
3 months: follow-up in clinic with VCSS, AVVQ, 
CIVIQ and EQ-5D as well as venous Duplex  
12 months: follow-up in clinic with VCSS, AVVQ, 
CIVIQ and EQ-5D as well as venous Duplex  
Pain Score immediately following endovenous 
ablation and pain score assessment again following 
tributary treatment (if applicable)