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Trial registered on ANZCTR


Registration number
ACTRN12620000208909p
Ethics application status
Submitted, not yet approved
Date submitted
23/01/2020
Date registered
20/02/2020
Date last updated
27/02/2020
Date data sharing statement initially provided
20/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Haemostatic Gel Prophylaxis for Post Duodenal Endoscopic Resection Bleeding
Scientific title
Randomised Controlled Trial of Haemostatic Gel Prophylaxis for Post Duodenal Endoscopic Mucosal Resection Bleeding In Patients with Advanced Mucosal Neoplasia in the Duodenum
Secondary ID [1] 300080 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced duodenal mucosal/submucosal neoplasia 315601 0
Condition category
Condition code
Oral and Gastrointestinal 313893 313893 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Surgery 314366 314366 0 0
Other surgery
Cancer 314367 314367 0 0
Bowel - Small bowel (duodenum and ileum)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Advanced endoscopic resection (ER) techniques such as endoscopic mucosal resection (EMR) have provided a minimally invasive alternative to surgery for curative management of advanced mucosal neoplasia. The safety profile and outcomes of ER techniques are significantly better than surgical resection however significant post resection bleeding remains an ongoing challenge. There is currently no consistently recommended strategy to reduce the risk of post-ER bleeding that has been adopted as standard of care.
ER in the duodenum carries the highest risk for for post ER bleeding based on anatomical location. This rate is particularly high with ER of and around the ampulla/ampullectomy (~20%).
A recently introduced haemostatic gel (Purastat, 3D-Matrix) that acts as a self assembling nanoparticle matrix has demonstrated efficacy as a topical haemostat in controlling oozing bleeding in a number of anatomical locations including applications in ENT, Gynaecology, and endoscopy.

All patients will be given high dose PPI prophylactically and undergo standard resection technique as outlined below for EMR and Ampullectomy. The control subjects will have these interventions ALONE, while the intervention arm will have these interventions in ADDITION to gel matrix.

EMR:
o Gelofusine + chromo of choice + 1:100,000 adrenaline in all injections unless adrenaline contraindicated
o Snare of choice but must use Endocut diathermy
o Intraprocedural haemostasis defined as clips only to active bleeding point or to area of injury not to close the entire defect
o Adjunctive therapy permitted for fibrosis/islands: avulsion,
o Salvage Purastat allowed in both arms if uncontrollable oozing bleeding intraprocedurally

Ampullectomy
o Resection of laterally spreading component as per duodenal EMR protocol
o Snare based resection of the ampulla without injection into the ampulla with the aim of en-bloc ampullary resection.
o Intraprocedural haemostasis as indicated/clinician preference however clips only to active bleeding point or to area of MP injury not to close the entire defect
o Routine placement of plastic PD stent (except if known pancreas divisum)
o Routine biliary stenting
o Salvage Purastat allowed in both arms if uncontrollable oozing bleeding intraprocedurally

We hypothesise that the application of the topical haemostatic gel to the duodenum will reduce the rate of clinically significant bleeding.
We will be applying aliquots of 1-5mLs of the gel matrix; the exact amount will be determined by the size of the defect remaining post excision of the target lesion. Gel will be applied endoscopically via the proceduralist until the entire defect has been covered.
Intervention code [1] 316350 0
Treatment: Other
Comparator / control treatment
All patients will be given high dose PPI prophylactically and undergo standard resection technique as outlined below for EMR and Ampullectomy. The control subjects will have these interventions ALONE, while the intervention arm will have these interventions in ADDITION to gel matrix.

EMR:
o Gelofusine + chromo of choice + 1:100,000 adrenaline in all injections unless adrenaline contraindicated
o Snare of choice but must use Endocut diathermy
o Intraprocedural haemostasis defined as clips only to active bleeding point or to area of injury not to close the entire defect
o Adjunctive therapy permitted for fibrosis/islands: avulsion,
o Salvage Purastat allowed in both arms if uncontrollable oozing bleeding intraprocedurally

Ampullectomy
o Resection of laterally spreading component as per duodenal EMR protocol
o Snare based resection of the ampulla without injection into the ampulla with the aim of en-bloc ampullary resection.
o Intraprocedural haemostasis as indicated/clinician preference however clips only to active bleeding point or to area of MP injury not to close the entire defect
o Routine placement of plastic PD stent (except if known pancreas divisum)
o Routine biliary stenting
o Salvage Purastat allowed in both arms if uncontrollable oozing bleeding intraprocedurally
Control group
Active

Outcomes
Primary outcome [1] 322286 0
Rate of delayed post-procedural bleeding requiring further intervention (such as blood transfusion, admission to hospital, or other blood products (such as platelets, fresh frozen plasma, prothrombinex)
This will be assessed clinically by the presence of upper gastrointestinal bleeding (such as melena or haematochezia) where patients were given blood products as documented in the medical record.
Timepoint [1] 322286 0
30 days post endoscopic procedure
Secondary outcome [1] 377970 0
Procedure related adverse events. This is a composite of
- delayed perforation (as identified on imaging such as CT or MRI, or surgically)
- procedure related hospitalisation
- Procedure related death (where the death is a direct result of the procedure or a complication of the procedure)
These will be assessed via review of the medical record for documented evidence of any of the adverse events mentioned above.
Timepoint [1] 377970 0
30 days post endoscopic procedure
Secondary outcome [2] 378028 0
Haemostatic gel measures
- volume of gel applied in mL
- volume of gel per cm^2 of lesion (mL/cm^2)
- total time (s) of gel being applied per mL of gel applied
- Successful application to entire post EMR defect (yes/no; as determined by the proceduralist)
Timepoint [2] 378028 0
Day 0
Secondary outcome [3] 379522 0
Procedure outcome (successful EMR) - as determined by the proceduralist as complete resection of the target lesion(s). This is determined at the time of the procedure by the endoscopist and will be documented in the procedure report.
Timepoint [3] 379522 0
30 days post endoscopic procedure

Eligibility
Key inclusion criteria
All patients must be
18 years old or above
Single agent (excluding aspirin) or multiple anti-thrombotic agent use ceased within 1 week prior to the procedure*

For patients with ampullary lesions;
- Single ampullary lesion
- 10mm or greater in size
- Resection via hot ampullectomy, inject/EMR of adjacent lateral spreading component
- Morphology: 0-Is, 0-IIa/b/c or combination

For patients with duodenal Lesions
- 2 or less lesions
- 15mm or greater
- Resection via hot EMR
- Morphology: 0-Is, 0-IIa/b/c or combination, submucosal lesions

*Antithrombotic therapy other than single agent aspirin is defined as
either 1) patients taking one of; warfarin, apixaban, rivaroxaban, dabigatran, clopidogrel,
prasugrel, asasantin, or any heparin based therapy, OR 2) multiple anti-thrombotic
agents (combination of any of the aforementioned therapies and/or aspirin).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Unable to provide informed consent
• Age <18 years old
• Pregnant
• Allergy to Purastat
• “Cold” EMR

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment will occur via either sealed opaque envelopes or central randomisation.
The final decision based on the two options is yet to be determined, however it will be one of the aforementioned methods.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
For the primary outcome of rates of clinically significant bleeding, we will use a Chi-squared analysis to assess the clinical significance of the rates of bleeding between the two groups, and provide the rates as a percentage for comparison.

For all other collected variables/outcomes we will use a combination of the following to compare groups:
- Descriptive/Summary statistics
- Hazard ratios for the primary outcomes with 95% confidence intervals
- Chi-squared analysis for categorical variables
- T-tests for normally distributed comparison of means

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment hospital [1] 15487 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 15488 0
Liverpool Day Surgery - Moorebank
Recruitment hospital [3] 15489 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [4] 15490 0
Port Macquarie Private Hospital - Port Macquarie
Recruitment hospital [5] 15491 0
Gold Coast University Hospital - Southport
Recruitment hospital [6] 15492 0
Royal Perth Hospital - Perth
Recruitment hospital [7] 15493 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [8] 15494 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [9] 15495 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [10] 15496 0
Concord Repatriation Hospital - Concord
Recruitment hospital [11] 15620 0
Sydney Adventist Hospital - Wahroonga
Recruitment postcode(s) [1] 28839 0
2170 - Liverpool
Recruitment postcode(s) [2] 28840 0
2170 - Moorebank
Recruitment postcode(s) [3] 28841 0
2444 - Port Macquarie
Recruitment postcode(s) [4] 28842 0
4215 - Southport
Recruitment postcode(s) [5] 28843 0
6000 - Perth
Recruitment postcode(s) [6] 28844 0
4029 - Herston
Recruitment postcode(s) [7] 28845 0
3050 - Parkville
Recruitment postcode(s) [8] 28846 0
3065 - Fitzroy
Recruitment postcode(s) [9] 28847 0
2139 - Concord
Recruitment postcode(s) [10] 29022 0
2076 - Wahroonga

Funding & Sponsors
Funding source category [1] 304527 0
Hospital
Name [1] 304527 0
Liverpool Hospital Gastroenterology Department
Address [1] 304527 0
Cnr Elizabeth and Goulburn St, Liverpool, NSW, 2170
Country [1] 304527 0
Australia
Primary sponsor type
Hospital
Name
Liverpool Hospital
Address
Cnr Elizabeth and Goulburn St, Liverpool, NSW, 2170
Country
Australia
Secondary sponsor category [1] 304815 0
None
Name [1] 304815 0
Address [1] 304815 0
Country [1] 304815 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 304960 0
South Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 304960 0
Cnr Elizabeth and Goulburn St, Liverpool, NSW, 2170
Ethics committee country [1] 304960 0
Australia
Date submitted for ethics approval [1] 304960 0
06/02/2020
Approval date [1] 304960 0
Ethics approval number [1] 304960 0
Submitted on the above date, not yet approved

Summary
Brief summary
This study aims to evaluate the effect of a gel on postoperative bleeding in patients undergoing endoscopic mucosal resection for advanced mucosal/submucosal neoplasia.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above, and are scheduled to undergo endoscopic mucosal resection (EMR) for ampullary lesions or duodenal lesions.

Study details
Participants in this study will be randomly allocated (by chance) to one of two groups. Participants in one group will undergo standard treatment for the prevention of bleeding, which involves routine endoscopic measures such as placing clips at sites of bleeding. Participants in the other group will have a haemostatic gel (Purastat, 3D-Matrix) applied endoscopically in addition to the standard measures such as the endoscopic clips.

Following the procedure, we will compare the rates of clinically significant bleeding between the two groups. We will also record and compare any adverse events. We hope that the gel can reduce the risk of post EMR bleeding.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98770 0
Dr Milan Bassan
Address 98770 0
Liverpool Hospital, Cnr Elizabeth and Goulburn St, Liverpool NSW, 2170
Country 98770 0
Australia
Phone 98770 0
+61 02 9601 7766
Fax 98770 0
Email 98770 0
milan.bassan@gmail.com
Contact person for public queries
Name 98771 0
Dr Martin Harb
Address 98771 0
Liverpool Hospital, Cnr Elizabeth and Goulburn St, Liverpool NSW, 2170
Country 98771 0
Australia
Phone 98771 0
+61 02 9601 7766
Fax 98771 0
Email 98771 0
martin.harb@health.nsw.gov.au
Contact person for scientific queries
Name 98772 0
Dr Martin Harb
Address 98772 0
Liverpool Hospital, Cnr Elizabeth and Goulburn St, Liverpool NSW, 2170
Country 98772 0
Australia
Phone 98772 0
+61 02 9601 7766
Fax 98772 0
Email 98772 0
martin.harb@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 6182 0
Study protocol
Citation [1] 6182 0
Link [1] 6182 0
Email [1] 6182 0
Other [1] 6182 0
This was created by Dr Milan Bassan, see attached word document
Summary results
No Results