Distal PancreatectomyPREPARENCT04220931
Intrapapillary Botulinum Toxin Injection for PREvention of Post-surgical PAncREactic Fistula
A study testing botulinum toxin injection in people with Distal Pancreatectomy and Postoperative Pancreatic Fistula, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Surgery is required for the treatment of many pancreatic conditions, either malignant or benign. Mortality of pancreatic surgery can be up to 3% even in expert centers. Morbidity is high, postoperative pancreatic fistula (POPF) being the main postoperative complication. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Distal Pancreatectomy, Postoperative Pancreatic Fistula
- What is being tested?
- botulinum toxin injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 460 participants
- Where
- 1 siteFrance
- Study dates
- 27 Mar 2023to 1 Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with scheduled distal pancreatectomy for any indication: open or laparoscopic distal pancreatectomy with or without splenectomy
- Age ≥ 18years
Who cannot join
- History of myasthenia gravis or Eaton-Lambert syndrome
- Inflammatory myositis <2 years or preexisting motor neuron disease or neuropathies
- ASA score > III
- Pregnancy or lactation
- Altered anatomy of the duodenum and/or the major papilla (prior surgery, prior endoscopic sphincterotomy)
- Scheduled pancreaticoduodenectomy (Whipple procedure)
Show all 23Show fewer
- Scheduled total pancreatectomy
- Scheduled central pancreatectomy
- Scheduled pancreatic enucleation
- Calcified chronic pancreatitis (suspected on preoperative cross-sectional imaging)
- Pancreas divisum (suspected on preoperative cross-sectional imaging)
- Toxin botulinum contraindications (hypersensitivity to albumin or to saccharose, infection or inflammation at the injection site concerned, generalized muscle weakness)
- Preoperative administration of somatostatin analogs: for long-acting somatostatin analogs, a 1-month washout period is necessary; for short-acting somatostatin analogs, a 24-hours washout period is necessary
- Any kind of surgical method to reinforce the pancreatic stump:
- Use of a bioabsorbable patch
- Use of fibrin glue
- Use of a ligament patch
- Tutorship, trusteeship
- Concurrent participation in other experimental trials
- Not Affiliation to the French social security
- Not Ability to give their consent and not written informed consent
- Distal pancreatectomy extended to neighbouring organs (except spleen and gallbladder) or to the vessels (celiac axis, portal vein)
- Secondary exclusion criteria: patients who did not have the planned surgery in less than 4 weeks after the botulinum toxin injection.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Alain Sauvanet, Prof contact
France1 site, 1 recruiting
- Recruiting
PRAT
Clichy, 92110
Frederic Prat, pr, frederic.prat@aphp.fr
About this study
Surgery is required for the treatment of many pancreatic conditions, either malignant or benign. Mortality of pancreatic surgery can be up to 3% even in expert centers. Morbidity is high, postoperative pancreatic fistula (POPF) being the main postoperative complication. In its current definition (drain output of any measurable fluid >= postoperative day 3 with amylase content >3 times the serum amylase activity and with clinical consequence), the incidence of postoperative PF is between 15 and 30 %. Most POPF resolve spontaneously but when refractory POPF occurs, it may lead to severe complications. POPF severity is graded as follows: grade B in case of change in medical management: infection without organ failure, specific medication (total parenteral nutrition, somatostatin analogs, antibiotics), persistent drainage > 3 weeks, angiographic procedure for bleeding, prolonged hospital stay; grade C in case of reoperation or PF-related organ failure or death.
No specific prophylactic treatment of POPF is currently recommended by clinical guidelines. In clinical research, many prophylactic strategies have been attempted with partial efficacy. Endoscopic pancreatic sphincterotomy with plastic stent placement is effective in pre-and postoperative management of pancreatic fistula but with the need of a highly competent interventional endoscopist. Intrapapillary botulinum toxin injection is believed to induce relaxation of the pancreatic sphincter, leading to a " pharmacological " pancreatic sphincterotomy without any morbidity.
A recent phase I/II prospective study has shown promising results in this indication, with no clinically relevant pancreatic fistula when botulinum toxin was injected. Based on this observation we hypothesize that intrapapillary botulinum toxin injection during an endoscopic procedure before surgery could be effective for the prevention of post-surgical pancreatic fistula
Read the detailed description
Surgery is required for the treatment of many pancreatic conditions, either malignant or benign. Mortality of pancreatic surgery can be up to 3% even in expert centers. Morbidity is high, postoperative pancreatic fistula (POPF) being the main postoperative complication. In its current definition (drain output of any measurable fluid >= postoperative day 3 with amylase content >3 times the serum amylase activity and with clinical consequence), the incidence of postoperative PF is between 15 and 30 %. Most POPF resolve spontaneously but when refractory POPF occurs, it may lead to severe complications. POPF severity is graded as follows: grade B in case of change in medical management: infection without organ failure, specific medication (total parenteral nutrition, somatostatin analogs, antibiotics), persistent drainage > 3 weeks, angiographic procedure for bleeding, prolonged hospital stay; grade C in case of reoperation or PF-related organ failure or death.
No specific prophylactic treatment of POPF is currently recommended by clinical guidelines. In clinical research, many prophylactic strategies have been attempted with partial efficacy. Endoscopic pancreatic sphincterotomy with plastic stent placement is effective in pre-and postoperative management of pancreatic fistula but with the need of a highly competent interventional endoscopist. Intrapapillary botulinum toxin injection is believed to induce relaxation of the pancreatic sphincter, leading to a " pharmacological " pancreatic sphincterotomy without any morbidity.
A recent phase I/II prospective study has shown promising results in this indication, with no clinically relevant pancreatic fistula when botulinum toxin was injected. Based on this observation we hypothesize that intrapapillary botulinum toxin injection during an endoscopic procedure before surgery could be effective for the prevention of post-surgical pancreatic fistula
This study will be a prospective, multicentric, phase III, superiority, controlled, randomized (1:1), open-label, clinical trial with two parallel arms (intrapapillary botulinum toxin versus standard care), using a PROBE (Prospective Randomized Open Blinded End-point) methodology.
Patients with scheduled distal pancreatectomy for any indication
Sources of funding for the trial : French Ministry supports this study by PHRC-N 2017.
The botulinum toxin provides by MERZ France (producer of Xeomin)
- Being tested
- botulinum toxin injection
- Keywords
- distal pancreatectomy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
botulinum toxin injectionDrug
injection of Botulinum toxin A 100 UI, single dose administration, in the major papilla, in the Oddi sphincter, during upper gastrointestinal endoscopy.
| Study group | Role | What they receive |
|---|---|---|
| botulinum toxin injection | Experimental | Injection of Botulinum toxin A 100 UI, single dose administration, in the major papilla, in the Oddi sphincter, during upper gastrointestinal endoscopy.
The endoscopic procedure will be performed under unconscious sedation with intravenous injection of propofol by an anesthesiologist. Receives: Drug: botulinum toxin injection |
| standard care | No intervention | standard care (no endoscopy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of postoperative pancreatic fistula
Clinically relevant POPF (grade B and C) in the 3 months after Distal Pancreatectomy
Measured: 3 months
Secondary outcomes (12)
number of postoperative pancreatic fistulas grade B
Grade of postoperative pancreatic fistulas B based on the ISGPF 2016 update
Measured: 3 months
number of postoperative pancreatic fistulas grade C
Grade of postoperative pancreatic fistulas C based on the ISGPF 2016 update
Measured: 3 months
Quantity of Biochemical leak after surgery
Biochemical leak after surgery
Measured: 3 months
number of Postoperative complications
Postoperative complications :
- intra-abdominal fluid collection
- delayed gastric emptying
- hemorrhage
- pancreatitis
- wound infection
- other infectious complication
Measured: 3 months
CLAVIEN-DINDO classification for post-surgical morbidity
CLAVIEN-DINDO classification for post-surgical morbidity
Measured: 3 months
Number of hospital days
Health economics endpoints : duration of hospital stay
Measured: 3 months
Number of hospital readmissions
Health economics endpoints : hospital readmissions
Measured: 3 months
Number of transfer to intensive care unit and the duration of these stays
Health economics endpoints : transfer to intensive care unit and the duration of these stays
Measured: 3 months
Number of fistularelated postoperative invasive procedures
Health economics endpoints : fistularelated postoperative invasive procedures
Measured: 3 months
overall costs of hospitalization
Health economics endpoints : overall costs
Measured: 3 months
Quality of life EQ-5D-5L questionnaire
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state : LEVEL 1: indicating no problem LEVEL 2: indicating slight problems LEVEL 3: indicating moderate problems LEVEL 4: indicating severe problems LEVEL 5: indicating unable to/extreme problems
Measured: 3 months
Number of sides effects (complications) related to the endoscopic botulinum toxin injection
number of sides effects (complications) related to the endoscopic botulinum toxin injection
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2020
- Study start27 Mar 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion1 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Distal PancreatectomyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 460 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Frederic Prat, prof, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04220931
- Sponsor's protocol ID
- P170913J
- Acronym
- PREPARE
- Status last verified
- Jul 2023
- First submitted
- 20 Dec 2019
- Last updated
- 10 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intrapapillary Botulinum Toxin Injection for PREvention of Post-surgical PAncREactic Fistula
- ClinicalTrials.gov ID
- NCT04220931
- Acronym / sponsor ID
- PREPARE / P170913J
- Keywords
- distal pancreatectomy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 460 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 27 Mar 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 1 Mar 2027 (estimated)
- First posted
- 7 Jan 2020 (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.
Surgery is required for the treatment of many pancreatic conditions, either malignant or benign. Mortality of pancreatic surgery can be up to 3% even in expert centers. Morbidity is high, postoperative pancreatic fistula (POPF) being the main postoperative complication. In its current definition (drain output of any measurable fluid >= postoperative day 3 with amylase content >3 times the serum amylase activity and with clinical consequence), the incidence of postoperative PF is between 15 and 30 %. Most POPF resolve spontaneously but when refractory POPF occurs, it may lead to severe complications. POPF severity is graded as follows: grade B in case of change in medical management: infection without organ failure, specific medication (total parenteral nutrition, somatostatin analogs, antibiotics), persistent drainage > 3 weeks, angiographic procedure for bleeding, prolonged hospital stay; grade C in case of reoperation or PF-related organ failure or death.
No specific prophylactic treatment of POPF is currently recommended by clinical guidelines. In clinical research, many prophylactic strategies have been attempted with partial efficacy. Endoscopic pancreatic sphincterotomy with plastic stent placement is effective in pre-and postoperative management of pancreatic fistula but with the need of a highly competent interventional endoscopist. Intrapapillary botulinum toxin injection is believed to induce relaxation of the pancreatic sphincter, leading to a " pharmacological " pancreatic sphincterotomy without any morbidity.
A recent phase I/II prospective study has shown promising results in this indication, with no clinically relevant pancreatic fistula when botulinum toxin was injected. Based on this observation we hypothesize that intrapapillary botulinum toxin injection during an endoscopic procedure before surgery could be effective for the prevention of post-surgical pancreatic fistula
Detailed description
Surgery is required for the treatment of many pancreatic conditions, either malignant or benign. Mortality of pancreatic surgery can be up to 3% even in expert centers. Morbidity is high, postoperative pancreatic fistula (POPF) being the main postoperative complication. In its current definition (drain output of any measurable fluid >= postoperative day 3 with amylase content >3 times the serum amylase activity and with clinical consequence), the incidence of postoperative PF is between 15 and 30 %. Most POPF resolve spontaneously but when refractory POPF occurs, it may lead to severe complications. POPF severity is graded as follows: grade B in case of change in medical management: infection without organ failure, specific medication (total parenteral nutrition, somatostatin analogs, antibiotics), persistent drainage > 3 weeks, angiographic procedure for bleeding, prolonged hospital stay; grade C in case of reoperation or PF-related organ failure or death.
No specific prophylactic treatment of POPF is currently recommended by clinical guidelines. In clinical research, many prophylactic strategies have been attempted with partial efficacy. Endoscopic pancreatic sphincterotomy with plastic stent placement is effective in pre-and postoperative management of pancreatic fistula but with the need of a highly competent interventional endoscopist. Intrapapillary botulinum toxin injection is believed to induce relaxation of the pancreatic sphincter, leading to a " pharmacological " pancreatic sphincterotomy without any morbidity.
A recent phase I/II prospective study has shown promising results in this indication, with no clinically relevant pancreatic fistula when botulinum toxin was injected. Based on this observation we hypothesize that intrapapillary botulinum toxin injection during an endoscopic procedure before surgery could be effective for the prevention of post-surgical pancreatic fistula
This study will be a prospective, multicentric, phase III, superiority, controlled, randomized (1:1), open-label, clinical trial with two parallel arms (intrapapillary botulinum toxin versus standard care), using a PROBE (Prospective Randomized Open Blinded End-point) methodology.
Patients with scheduled distal pancreatectomy for any indication
Sources of funding for the trial : French Ministry supports this study by PHRC-N 2017.
The botulinum toxin provides by MERZ France (producer of Xeomin)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| botulinum toxin injection | Experimental | Drug: botulinum toxin injectionInjection of Botulinum toxin A 100 UI, single dose administration, in the major papilla, in the Oddi sphincter, during upper gastrointestinal endoscopy. The endoscopic procedure will be performed under unconscious sedation with intravenous injection of propofol by an anesthesiologist. |
| standard care | No intervention | –standard care (no endoscopy) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with scheduled distal pancreatectomy for any indication: open or laparoscopic distal pancreatectomy with or without splenectomy
- Age ≥ 18years
Key exclusion criteria (23 listed)
- History of myasthenia gravis or Eaton-Lambert syndrome
- Inflammatory myositis <2 years or preexisting motor neuron disease or neuropathies
- ASA score > III
- Pregnancy or lactation
- Altered anatomy of the duodenum and/or the major papilla (prior surgery, prior endoscopic sphincterotomy)
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 |
|---|---|---|
| botulinum toxin injectioninjection of Botulinum toxin A 100 UI, single dose administration, in the major papilla, in the Oddi sphincter, during upper gastrointestinal endoscopy. | Drug | botulinum toxin injection |
Primary outcome
number of postoperative pancreatic fistula
Time frame: 3 months
Clinically relevant POPF (grade B and C) in the 3 months after Distal Pancreatectomy
12 secondary outcomes
number of postoperative pancreatic fistulas grade B
Time frame: 3 months
number of postoperative pancreatic fistulas grade C
Time frame: 3 months
Quantity of Biochemical leak after surgery
Time frame: 3 months
number of Postoperative complications
Time frame: 3 months
CLAVIEN-DINDO classification for post-surgical morbidity
Time frame: 3 months
Number of hospital days
Time frame: 3 months
Number of hospital readmissions
Time frame: 3 months
Number of transfer to intensive care unit and the duration of these stays
Time frame: 3 months
Number of fistularelated postoperative invasive procedures
Time frame: 3 months
overall costs of hospitalization
Time frame: 3 months
Quality of life EQ-5D-5L questionnaire
Time frame: 3 months
Number of sides effects (complications) related to the endoscopic botulinum toxin injection
Time frame: 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2023.
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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.
Alain Sauvanet, Prof contact
Frederic Prat, prof principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing botulinum toxin injection in people with Distal Pancreatectomy and Postoperative Pancreatic Fistula, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 2 inclusion and 23 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: looking for participants now, as of the sponsor's last update on 10 Jul 2023. 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 France. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Frederic Prat, Prof (0033(1)40875663, frederic.prat@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of postoperative pancreatic fistula (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jul 2023.