Post Operative Pancreatic FistulaPhase 1POPFNCT03891225
Efficacy of Amniotic Membrane Over Pancreatic Anastomosis After Pancreaticoduodenenctomy to Preventing Pancreatic Fistula
A Phase 1 study testing Amniotic Membrane implantation in people with Post Operative Pancreatic Fistula and Pancreatic Resection, run by Casa di Cura Dott. Pederzoli at 1 site in Italy.
Trial summary
Post-operative pancreatic fistula (POPF) after pancreatic resection is a potentially life-threatening complication occuring in up to 27% of patients undergoing a pancreatic resection. Despite several strategies have been proposed further improvements are needed. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Post Operative Pancreatic Fistula, Pancreatic Resection, Biological Dressing
- What is being tested?
- Amniotic Membrane implantation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 25 Mar 2019to 20 Dec 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18 and 85 years
- Undergone to Pancreatico-duodenectomy with high FRS (>=5)
- Adeguate consent
Who cannot join
- Total pancreatectomy
- Pancreatic anastomosis different from pancreo-jejunal anastomosis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy of Amniotic Membrane Implantation Over Pancreo-jejunal Anastomosis After Pancreaticoduodenectomy in Reducing Post-operative Pancreatic Fistula POPF.
Post-operative pancreatic fistula (POPF) after pancreatic resection is a potentially life-threatening complication occuring in up to 27% of patients undergoing a pancreatic resection. Despite several strategies have been proposed further improvements are needed. Many studies suggest that amniotic membrane(AM) implantation is effective in tissue regeneration and prevention of fluid leakage at many surgical sites. However,the implantation of AM has never been used in pancreatic surgery.
After having completed the first case of implantation of AM we proceed with this pilot study to determine in 20 consecutive patients undergone to pancreaticoduodenectomy (PD) with high risk of POPF, the efficacy of AM in reducing this event and the related morbidity.
Read the detailed description
Twenty consecutive patients candidated to PD regardless the diagnosis will be enrolled if presenting an high Fistula Risk Score. Enrollement will be done in O.R. after frozen section of the pancreas. The AM is provided by Fondazione Banca dei Tessuti di Treviso Onlus. The placenta is sourced from donors undergoing caesarean sections and processed shortly after retrieval, donors are evaluated according to Italian requirements. The AM is carefully detached from the chorion and rinsed with sterile saline solution, flattened on a nitrocellulose membrane filter (Merck Millipore), with its stromal side facing down, in contact with the filter. The AM is then immersed in a cocktail of antibiotics then cut into patches and immersed in cryopreservant solution. Cryopreservation was achieved using a programmable cryogenic freezer (Planer KryoSave Integra, 750-30), which triggers a controlled cooling rate. The AM patches were stored in vapor-phase liquid nitrogen. Thirty minutes before its use, the AM was defrozen and washed with saline. A 10x15cm MA patch was placed around the pancreatic anastomoses starting from the posterior surface. The caudal and the cranial flap were overlapped on the anterior surface to wrap the anastomosis. The membrane was than fixed with 4-0 Monocryl sutures at the jejunal surface and at the peri-pancreatic tissue. Then an end-to-side bilio-enteric anastomosis was carried out. The reconstruction was completed by an end-to-side antecolic duodenojejunostomy. At the end of the procedure, two drains were placed ventral and dorsal to the PJ, without friction with the AM.
In the postoperative period will be evaluated: morbidity according to Clavien Dindo classification with attention to clinical relevant pancreatic fistula, bleeding, need of reintervention, surgical site infection, multi drug resistant infection and mortality. Costs and postoperative staying will be monitored as well.
Student t test, Mann Whitney and Chi square will be used for statistical analysis.
- Being tested
- Amniotic Membrane implantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amniotic Membrane implantationProcedure or surgery
Surgical procedure will be performed with Longemire Traverso technique. At the end of all pancreatic, biliary and duodenal anastomosis, the AM will be implanted.
| Study group | Role | What they receive |
|---|---|---|
| Amniotic Membrane implantation Arm | Experimental | All consecutive patients undergone pancreaticoduodenectomy with high FRS will be treated with implantation of AM, by overlapping it over the pancreo-jejunal anastomosis. Receives: Procedure: Amniotic Membrane implantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
postoperative complications
clinical relevant pancreatic fistula, intra-abdominal collection, acute pancreatitis, SSI, need for reintervention, mortality
Measured: up to 90 days after surgery
Secondary outcomes (1)
correlation between microscopic pancreatic fibrosis and CR POPF
the absence of microscopic fibrosis in a macroscopically soft pancreas may be related to higher risk of CR POPF and therefore may suggest implementation of anastomotic protecion (ie. the AM)
Measured: 90 days from surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2019
- Study start25 Mar 2019
- Primary completion30 Sep 2020
- Study completion20 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Post Operative Pancreatic FistulaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Pilot study
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Casa di Cura Dott. Pederzoli
- Sponsor type
- University, hospital or other
- Collaborators
- Fondazione Banca dei Tessuti di Treviso onlus
- Responsible party
- Principal investigator, Isabella Frigerio, Casa di Cura Dott. Pederzoli
- Investigators
- ISABELLA FRIGERIO, Principal investigator, PEDERZOLI HOSPITAL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03891225
- Sponsor's protocol ID
- 2039CESC
- Acronym
- POPF
- Status last verified
- Jan 2021
- First submitted
- 25 Mar 2019
- Last updated
- 6 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: UPON REQUEST
Publications
Pulvirenti A, Marchegiani G, Pea A, Allegrini V, Esposito A, Casetti L, Landoni L, Malleo G, Salvia R, Bassi C. Clinical Implications of the 2016 International Study Group on Pancreatic Surgery Definition and Grading of Postoperative Pancreatic Fistula on 775 Consecutive Pancreatic Resections. Ann Surg. 2018 Dec;268(6):1069-1075. doi: 10.1097/SLA.0000000000002362.
PubMed 28678062McMillan MT, Vollmer CM Jr, Asbun HJ, Ball CG, Bassi C, Beane JD, Berger AC, Bloomston M, Callery MP, Christein JD, Dixon E, Drebin JA, Castillo CF, Fisher WE, Fong ZV, Haverick E, House MG, Hughes SJ, Kent TS, Kunstman JW, Malleo G, McElhany AL, Salem RR, Soares K, Sprys MH, Valero V 3rd, Watkins AA, Wolfgang CL, Behrman SW. The Characterization and Prediction of ISGPF Grade C Fistulas Following Pancreatoduodenectomy. J Gastrointest Surg. 2016 Feb;20(2):262-76. doi: 10.1007/s11605-015-2884-2. Epub 2015 Jul 11.
PubMed 26162925Patel K, Teta A, Sukharamwala P, Thoens J, Szuchmacher M, DeVito P. External pancreatic duct stent reduces pancreatic fistula: a meta-analysis and systematic review. Int J Surg. 2014;12(8):827-32. doi: 10.1016/j.ijsu.2014.06.008. Epub 2014 Jul 6.
PubMed 25003575Callery MP, Pratt WB, Kent TS, Chaikof EL, Vollmer CM Jr. A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg. 2013 Jan;216(1):1-14. doi: 10.1016/j.jamcollsurg.2012.09.002. Epub 2012 Nov 2.
PubMed 23122535Lin SD, Lai CS, Hou MF, Yang CC. Amnion overlay meshed skin autograft. Burns Incl Therm Inj. 1985 Jun;11(5):374-8. doi: 10.1016/0305-4179(85)90102-0.
PubMed 3896420Talmi YP, Sigler L, Inge E, Finkelstein Y, Zohar Y. Antibacterial properties of human amniotic membranes. Placenta. 1991 May-Jun;12(3):285-8. doi: 10.1016/0143-4004(91)90010-d.
PubMed 1754577Barski D, Gerullis H, Ecke T, Varga G, Boros M, Pintelon I, Timmermans JP, Winter A, Bagner JW, Otto T. Repair of a vesico-vaginal fistula with amniotic membrane - Step 1 of the IDEAL recommendations of surgical innovation. Cent European J Urol. 2015;68(4):459-61. doi: 10.5173/ceju.2015.683. Epub 2015 Nov 13.
PubMed 26855802Knight BC, Kausar A, Manu M, Ammori BA, Sherlock DJ, O'Reilly DA. Evaluation of surgical outcome scores according to ISGPS definitions in patients undergoing pancreatic resection. Dig Surg. 2010;27(5):367-74. doi: 10.1159/000313693. Epub 2010 Oct 13.
PubMed 20938180
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Amniotic Membrane Implantation Over Pancreo-jejunal Anastomosis After Pancreaticoduodenectomy in Reducing Post-operative Pancreatic Fistula POPF.
- ClinicalTrials.gov ID
- NCT03891225
- Acronym / sponsor ID
- POPF / 2039CESC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Casa di Cura Dott. PederzoliUniversity, hospital or other
- Collaborators
- Fondazione Banca dei Tessuti di Treviso onlus
- Study start
- 25 Mar 2019 (actual)
- Primary completion
- 30 Sep 2020 (actual)
- Study completion
- 20 Dec 2020 (actual)
- First posted
- 26 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Post-operative pancreatic fistula (POPF) after pancreatic resection is a potentially life-threatening complication occuring in up to 27% of patients undergoing a pancreatic resection. Despite several strategies have been proposed further improvements are needed. Many studies suggest that amniotic membrane(AM) implantation is effective in tissue regeneration and prevention of fluid leakage at many surgical sites. However,the implantation of AM has never been used in pancreatic surgery.
After having completed the first case of implantation of AM we proceed with this pilot study to determine in 20 consecutive patients undergone to pancreaticoduodenectomy (PD) with high risk of POPF, the efficacy of AM in reducing this event and the related morbidity.
Detailed description
Twenty consecutive patients candidated to PD regardless the diagnosis will be enrolled if presenting an high Fistula Risk Score. Enrollement will be done in O.R. after frozen section of the pancreas. The AM is provided by Fondazione Banca dei Tessuti di Treviso Onlus. The placenta is sourced from donors undergoing caesarean sections and processed shortly after retrieval, donors are evaluated according to Italian requirements. The AM is carefully detached from the chorion and rinsed with sterile saline solution, flattened on a nitrocellulose membrane filter (Merck Millipore), with its stromal side facing down, in contact with the filter. The AM is then immersed in a cocktail of antibiotics then cut into patches and immersed in cryopreservant solution. Cryopreservation was achieved using a programmable cryogenic freezer (Planer KryoSave Integra, 750-30), which triggers a controlled cooling rate. The AM patches were stored in vapor-phase liquid nitrogen. Thirty minutes before its use, the AM was defrozen and washed with saline. A 10x15cm MA patch was placed around the pancreatic anastomoses starting from the posterior surface. The caudal and the cranial flap were overlapped on the anterior surface to wrap the anastomosis. The membrane was than fixed with 4-0 Monocryl sutures at the jejunal surface and at the peri-pancreatic tissue. Then an end-to-side bilio-enteric anastomosis was carried out. The reconstruction was completed by an end-to-side antecolic duodenojejunostomy. At the end of the procedure, two drains were placed ventral and dorsal to the PJ, without friction with the AM.
In the postoperative period will be evaluated: morbidity according to Clavien Dindo classification with attention to clinical relevant pancreatic fistula, bleeding, need of reintervention, surgical site infection, multi drug resistant infection and mortality. Costs and postoperative staying will be monitored as well.
Student t test, Mann Whitney and Chi square will be used for statistical analysis.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Pilot study
| Arm | Type | Receives |
|---|---|---|
| Amniotic Membrane implantation Arm | Experimental | Procedure: Amniotic Membrane implantationAll consecutive patients undergone pancreaticoduodenectomy with high FRS will be treated with implantation of AM, by overlapping it over the pancreo-jejunal anastomosis. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age between 18 and 85 years
- Undergone to Pancreatico-duodenectomy with high FRS (>=5)
- Adeguate consent
Key exclusion criteria (2 listed)
- Total pancreatectomy
- Pancreatic anastomosis different from pancreo-jejunal anastomosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amniotic Membrane implantationSurgical procedure will be performed with Longemire Traverso technique. At the end of all pancreatic, biliary and duodenal anastomosis, the AM will be implanted. | Procedure or surgery | Amniotic Membrane implantation Arm |
Primary outcome
postoperative complications
Time frame: up to 90 days after surgery
clinical relevant pancreatic fistula, intra-abdominal collection, acute pancreatitis, SSI, need for reintervention, mortality
1 secondary outcome
correlation between microscopic pancreatic fibrosis and CR POPF
Time frame: 90 days from surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2021.
- Background: PubMed 28678062Pulvirenti A, Marchegiani G, Pea A, Allegrini V, Esposito A, Casetti L, Landoni L, Malleo G, Salvia R, Bassi C. Clinical Implications of the 2016 International Study Group on Pancreatic Surgery Definition and Grading of Postoperative Pancreatic Fistula on 775 Consecutive Pancreatic Resections. Ann Surg. 2018 Dec;268(6):1069-1075. doi: 10.1097/SLA.0000000000002362.
- Background: PubMed 26162925McMillan MT, Vollmer CM Jr, Asbun HJ, Ball CG, Bassi C, Beane JD, Berger AC, Bloomston M, Callery MP, Christein JD, Dixon E, Drebin JA, Castillo CF, Fisher WE, Fong ZV, Haverick E, House MG, Hughes SJ, Kent TS, Kunstman JW, Malleo G, McElhany AL, Salem RR, Soares K, Sprys MH, Valero V 3rd, Watkins AA, Wolfgang CL, Behrman SW. The Characterization and Prediction of ISGPF Grade C Fistulas Following Pancreatoduodenectomy. J Gastrointest Surg. 2016 Feb;20(2):262-76. doi: 10.1007/s11605-015-2884-2. Epub 2015 Jul 11.
- Background: PubMed 25003575Patel K, Teta A, Sukharamwala P, Thoens J, Szuchmacher M, DeVito P. External pancreatic duct stent reduces pancreatic fistula: a meta-analysis and systematic review. Int J Surg. 2014;12(8):827-32. doi: 10.1016/j.ijsu.2014.06.008. Epub 2014 Jul 6.
- Background: PubMed 23122535Callery MP, Pratt WB, Kent TS, Chaikof EL, Vollmer CM Jr. A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J Am Coll Surg. 2013 Jan;216(1):1-14. doi: 10.1016/j.jamcollsurg.2012.09.002. Epub 2012 Nov 2.
- Background: PubMed 3896420Lin SD, Lai CS, Hou MF, Yang CC. Amnion overlay meshed skin autograft. Burns Incl Therm Inj. 1985 Jun;11(5):374-8. doi: 10.1016/0305-4179(85)90102-0.
- Background: PubMed 1754577Talmi YP, Sigler L, Inge E, Finkelstein Y, Zohar Y. Antibacterial properties of human amniotic membranes. Placenta. 1991 May-Jun;12(3):285-8. doi: 10.1016/0143-4004(91)90010-d.
- Background: PubMed 26855802Barski D, Gerullis H, Ecke T, Varga G, Boros M, Pintelon I, Timmermans JP, Winter A, Bagner JW, Otto T. Repair of a vesico-vaginal fistula with amniotic membrane - Step 1 of the IDEAL recommendations of surgical innovation. Cent European J Urol. 2015;68(4):459-61. doi: 10.5173/ceju.2015.683. Epub 2015 Nov 13.
- Background: PubMed 20938180Knight BC, Kausar A, Manu M, Ammori BA, Sherlock DJ, O'Reilly DA. Evaluation of surgical outcome scores according to ISGPS definitions in patients undergoing pancreatic resection. Dig Surg. 2010;27(5):367-74. doi: 10.1159/000313693. Epub 2010 Oct 13.
- Individual participant dataSharing planned: Undecided. UPON REQUEST
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ISABELLA FRIGERIO principal investigator
PEDERZOLI HOSPITAL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Amniotic Membrane implantation in people with Post Operative Pancreatic Fistula and Pancreatic Resection, run by Casa di Cura Dott. Pederzoli at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
postoperative complications (time frame: up to 90 days after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03891225, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2021.