Infant and Child European Cryoablation Project ICECaP
Conditions: Therapy, Soft Tissue Lesion, Cryoablation, Pediatric
Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust

 
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Infant and Child European Cryoablation Project  
 
 
 
Study ID: 18BB37 
 
 
 
 
 
 
 
Study Protocol 
 
Date of most recent review: 18th December 2020 
 

 
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Infant and Child European Cryoablation Project  
protocol 
 
 
STUDY INVESTIGATOR(S)  
 
Principal Investigator:  
Dr Alex Barnacle BM MRCP FRCR1 
 
Co-Investigator: 
 
Dr Premal Patel MBBS MRCS FRCR1 
 
 
 
1. Paediatric Interventional Radiologist, Department of Radiology, Great Ormond 
Street Hospital, London WC1N 3JH, UK  
 
 
1. SUMMARY  
A registry to audit the current range of applications, technical success rate, safety 
profile, complication rate and efficacy of cryoablation procedures being performed in 
children in the United Kingdom. 
 
2. BACKGROUND  
 
Cryoablation involves image-guided insertion of single-use specialised needles or 
probes through the skin into a soft tissue or bone lesion. The base unit is connected 
to the probe(s) and generates cyclical freezing and thawing of the tissues at the 
probe tip(s) via exchange of highly pressurised gases through the probe lumen(s). 
Extreme freezing and thawing of the lesion causes permanent tissue destruction 
through both mechanical disruption of tissue membranes and one or more secondary 
immune responses.  
Cryoablation is one of several minimally invasive ablative techniques used to reduce 
the size of or to eradicate soft tissue and bone lesions. Ablative techniques are now 
an accepted standard of care for many benign and malignant lesions in adult 
practice. Cryoablation is widely used in the management of renal cell carcinoma, as 
recognised by NICE, with long-term outcomes matching surgical resection [1]. 
 
The advantages of cryoablation over surgery, particularly in a paediatric population, 
are: 
• 
Minimally invasive approach, therefore suitable for day case procedures and 
almost scarless 
• 
Significantly faster recovery times compared to complex surgical debulking 
• 
Minimal complication rates compared to surgery (less risk to nerves, blood 
vessels and critical solid organ) 
• 
Affords excellent pain relief (has an independent role in chronic pain 
management)  
 

 
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To date the use of cryoablation in children remains novel and under reported [2,3]. 
The purpose of this registry is to audit the current range of applications, technical 
success rate, safety profile, complication rate and efficacy of cryoablation procedures 
in children. This registry will, as a minimum, clarify current practice and outcomes 
within individual centres, allowing teams to audit and benchmark their own 
procedures and aims to align practice amongst individual hospitals. A registry will 
provide a body of evidence to establish parameters for best practice and may 
highlight conditions that respond better or worse than others to this novel therapy. 
The audit may lead to a clinical trial for the treatment of one or more specific 
conditions but in the interim aims to provide evidence for the efficacy and safety of 
the procedure and protect against indiscriminate use of this treatment modality in 
children in the future. 
References: 
1. www.nice.org.uk/guidanceIPG402  
2. Shaikh R, Alomari AI, Kerr CL, Miller P, Spencer SA. Cryoablation in fibro-
adipose vascular anomaly (FAVA): a minimally invasive treatment option. 
Pediatr Radiol. 2016 Jul;46(8):1179-86 
3. Whitmore M, Hawkins C, Prologo J, et al. Cryoablation of osteoid osteoma in 
the pediatric and adolescent population. J Vasc Interv Radiol 2016 
Feb;27(2):232-7 
 
 
 
3. AIM(S) OF STUDY 
 
Principle aim:  
Establish feasibility and safety of cryoablation in children 
 
Secondary aims:  
Assess response to treatment (as measured by change in 
lesion size and/or change in symptomatology) post treatment   
 
 
4. OBJECTIVES   
 
1. To identify all cryoablation procedures in children in our institution.  
2. Invite other centres offering cryoablation in children to participate by 
submitting data via the online registry 
3. To collect data via an online registry 
4. To analyse the data to establish the safety and efficacy of this procedure in 
children and to identify trends in outcomes for different conditions treated 
5. To establish guidelines for best practice regarding cryoablation treatment in 
children 
 
 
5. STUDY DESIGN  
This is a prospective multi-centre, open, non-controlled repeat treatment registry and 
data collection in collaboration with other individual hospitals. The registry is based 

 
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with Great Ormond Street Hospital NHS Foundation Trust; other centres in the UK 
and Europe will be invited to participate. All such centres will be subject to their 
institution’s audit and ethics processes 
The registry will consist of a robust, multi-centre data collection system to support 
and establish the treatment pathway, safety parameters and outcomes of paediatric 
cryoablation. The registry aims to collect standardised data from all centres 
performing cryoablation in children to allow robust audit of this procedure and its 
outcomes. Multiple data sets will be collected and entered into an anonymised web-
based host. The registry is designed with the patient at the centre of the data 
collection. Anonymised data will be analysed collectively but will ultimately be owned 
and retained by individual Trusts.  
 
6. STUDY SETTING/LOCATION 
 
The registry is based at Great Ormond Street Hospital for Children NHS Foundation 
Trust. Data from all cryoablation procedures will be entered in this registry. Other 
Trusts will be encouraged to submit data to the same registry. 
 
 
7. STUDY POPULATION  
 
All children in whom a clinical decision is made to treat with percutaneous 
cryoablation 
 
 
8. ELIGIBILITY CRITERIA 
 
8a. Inclusion criteria  
All children in whom a clinical decision is made to treat with percutaneous 
cryoablation, to include those in whom cryoablation was not technically or clinically 
possible at any stage. 
 
8b. Exclusion criteria 
 
1. Subjects over the age of 18 years. 
2. Any subject whose clinical management evolves so that treatment modalities 
other than cryoablation are offered instead. 
 
 
9. STUDY OUTCOMES 
 
9a. Primary Outcome 
 
Occurrence and severity of complications arising from cryoablation treatment 
 
 
9b. Secondary Outcome(s) 
 
1. Occurrence and causes of procedural/technical failure of the procedure 

 
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2. Where relevant, change in maximal diameter of lesion following treatment, as 
measured on ultrasound or MRI, comparing pre-treatment diameter to 
diameter at 2 years.  
3. Where relevant, change in symptomatology post treatment, as assessed by 
quality of life questionnaires and visual analog scales. 
4. Where relevant, change in function post treatment, as assessed by clinical 
review and physiotherapy assessment. 
 
 
10. STUDY PROCEDURES  
 
10a. Recruitment of participants 
 
Data from all cryoablation procedures performed in our institution will be entered into 
the registry. Data from procedures at other UK institutions may also be submitted.  
 
10b. Randomisation  
 
This is a non-randomised study. 
 
10c. Study procedure  
 
Data will be entered into an online-based registry designed for this study. The 
registry is designed and managed by Obsidian Health Ltd and funded by 
Biocompatibles UK Ltd.  
 
The following dataset is an indication of the data items that will be collected within 
the registry. The registry is not limited to these items and the items and data format 
can be changed before or during the registry. 
 
Schema 
 
• 
Patient 
• 
Patient has Diagnosis 
• 
Patient has one or more Treatments 
• 
Patient has one or more Follow-ups 
• 
Patient has one or more Complications 
• 
Patient has one or more Post-ops 
 
Data items 
 
Data item 
Data type 
 
 
Patient 
 
Patient identifier 
Local pseudonym 
Date of Birth ( 0 - 18) 
Month and year only 
Gender 
List 
Weight (Kg) 
Float 

 
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ASA score (anaesthetic risk)  
1 - 4 
Integer 
 
 
Diagnosis 
 
Diagnosis 
List 
Comorbidities 
List 
Biopsy proven? 
Y/N 
Snomed code 
List 
Lesion anatomical site: limb, 
thorax, head and neck, 
abdomen, pelvis (need more 
detail here) 
List 
Lesion tissue involvement: 
Fat/bone/muscle/other 
LIst 
 
 
Pre-operative information 
 
 
Length of symptoms 
already 
 
Months 
Imaging (MRI, US, other) 
List 
Symptoms 
 
List 
Other treatments tried 
List 
 
 
Treatment 
 
Treatment date 
Date 
Pre-op  
List 
Size of lesion 
Float [possibly 3 floats] 
Symptoms 
List 
No of probes 
Integer 
Freeze time* 
Float 
Thaw time* 
Float 
Cryoablation system 
probe type(s) 
 
List [may need updating as 
new systems come onto 
market] 
No. of freeze/thaw cycles  
 
Radio 
Thaw type [active or passive] 
 
Radio 
% power during freeze cycle  
 
*freeze and thaw time for each 
cycle 
 

 
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Technical success  
Binary 
If technical success no -  
reason 
List +/- text 
Length of inpatient stay 
 
Any medical support required 
(list, such as iv analgesia) 
 
 
 
Immediate complications 
Multi-list 
 
 
Follow-up at 3 mths, 6 mths, 
1 year, 2 years 
 
Follow-up date 
Date 
Imaging 
List 
Size of lesion 
Float 
Symptoms 
List 
 
 
Complications at follow up 
 
 
Complication 
Multi-list 
Onset 
Duration of problem 
Any treatment given 
Resolved? 
 
 
 
 
10e. Patient safety  
 
Any adverse events related to a cryoablation procedure will be medically managed 
as per clinical need. All such events will be recorded, reported and managed 
according to the institution’s risk management system, alongside any data collection 
pertaining to this study.  
 
10f. Adverse events, Serious Adverse Events and Product Malfunctions  
An adverse event (AE) is defined as any untoward or unfavourable medical 
occurrence in a human patient or clinical trial subject administered a medicinal 
product, including any abnormal sign (for example, abnormal physical exam or 
laboratory finding), symptom, or disease, temporally associated with the patient’s 
participation in the research, and which does not necessarily have a causal 
relationship with this treatment (study medication, application of the study device, 
etc.) or study participation. It includes all adverse events regardless of seriousness or 
relatedness.  
 
A serious adverse event (SAE) is defined as an adverse event that  
a) Results in death 

 
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b) Led to a serious deterioration in health that either: 
I. 
Results in a life-threatening illness or injury, or 
II. 
Results in a permanent impairment of a body structure or a body 
function, or 
III. 
Requires in-patient hospitalization or prolongation of existing 
hospitalization, or 
IV. 
Results in medical or surgical intervention to prevent life threatening 
illness or injury or permanent impairment to a body structure or a body 
function.  
V. 
Results in a persistent or significant disability/incapacity or substantial 
disruption of the ability to conduct normal life functions. 
c) Led to fetal distress, foetal death or a congenital abnormality or birth defect 
 
A product malfunction is defined as a failure of the device to meet its performance 
specifications, essential function or otherwise perform as intended. Performance 
specifications include all claims made in the labelling for the device. The essential 
function of a device refers not only to the device's labelled use, but for any use widely 
prescribed within the practice of medicine. 
 
Reporting of Adverse Events, Serious Adverse Events and Device 
Malfunctions 
The Institution and/or the Sponsor-Investigator shall report all and any serious 
adverse events, product malfunctions or quality complaints (regardless of causality) 
that they become aware of in relation to the Product and/or the investigation to BTG.  
 
All reports will be exchanged in English and Sponsor-Investigator will also provide 
BTG with such information and reasonable assistance as may be requested by BTG 
to allow BTG to comply with their obligations.   
 
The Institution and/or the Sponsor-Investigator shall report all SAEs and incidents 
impacting patient safety to ICardioQAComplaints@bsci.com. 
 
SAEs 
.  
 
SAEs 
The Sponsor-Investigator will report SAEs within one business day to enable BTG 
to comply with their obligations as the device manufacturer, under applicable laws 
and regulations. 
All reports will contain the following, if available: 
• 
Study title and name of the Sponsor-Investigator.  
• 
Patient number 
• 
Adverse event number 
• 
Date of event occurrence/date notified 
• 
Product details 
o Product name/ part number 
o Size / dose  
o Batch / lot number 
• 
Adverse event details along with comprehensive event description  
• 
Action(s) taken to treat or resolve the event 

 
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• 
Outcome 
• 
Investigators opinion of causality of event i.e. related to 
o Drug  
o Device 
o Procedure 
• 
Product returned to Galil if applicable 
 
Device Malfunctions 
The Institution and/or the Sponsor-Investigator shall report all device malfunctions 
and/or quality complaints to ICardioQAComplaints@bsci.com within one business 
day of becoming aware of the issue. 
 
 
10g. Data monitoring   
 
Data will be reviewed by the co-investigators at a minimum of 6 month intervals. 
Procedural data will be collected for 3 years and follow up data will continue to be 
collected for a further 2 years. The registry plans to close after 5 years but this could 
be extended. Data analysis will be completed by 6 months post closure of the 
registry. 
 
See Appendix 1 [Obsidian Data Security Protocol] for details of data storage and 
management by Obsidian Health Ltd.  
 
 
11. STATISTICAL CONSIDERATIONS AND DATA ANALYSIS 
 
Upon completion of recruitment and follow up, the data will be subject to uni-variate 
and multi-variate analysis. Statistical analysis support will be provided by Obsidian 
Health Ltd but may also include other sources of statistical advice and expertise.  
 
 
12. ETHICAL CONSIDERATIONS  
 
We will conduct this study in full conformance with principles of the “Declaration of 
Helsinki”, Good Clinical Practice (GCP) and within the laws and regulations of the 
United Kingdom.  
 
The study is registered with the institution’s audit program; the institution’s audit 
committee have confirmed that formal ethics approval is not required for this study as 
it is an audit not a research study.   
 
See Appendix 1 [Obsidian Data Security Protocol] for details of data storage and 
management by Obsidian Health Ltd.  
 
We have considered the potential risks and proposed benefits of the study 
procedures, the priority of the participants’ interests over those of science or of 
society and how those interests will be safeguarded. All subjects will be offered 
cryoablation based on clinical need, as assessed by the multidisciplinary clinical 
team in our institution and as discussed and agreed with the patient and their 
family/guardian. The cryoablation procedure, its timing and its risks will not be altered 

 
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by entry into this registry. Children and families may be concerned that if they decline 
to participate in the study, this may affect the subject’s clinical care. They will be 
actively reassured that this is not the case; age-appropriate fact sheets and consent 
forms have been designed to make this clear and will be used throughout the study.   
 
 
13. OUTCOMES AND SIGNIFICANCE 
 
The results of this study will be shared with other participating centres and selected 
anonymised data will be made available to Boston Scientific Corporation, as owner of 
it's subsidiary Biocompatibles UK Ltd, who fund the study. The data will be used to 
establish best practice. Adverse outcomes will be investigated and used to modify 
the technique for future procedures. The study aims to highlight any conditions that 
respond significantly well or not to this procedure and will promote any such findings 
to ensure children are offered the best treatment available.  
 
The co-investigators plan to present the outcomes at the annual scientific meeting of 
the Society for Pediatric Interventional Radiology and other relevant scientific forums 
and publish the outcomes in relevant scientific journal(s). 
 
14. APPENDICES 
 
1. Obsidian Health Ltd Data Security Protocol