PREPARE - Intrapapillary botulinum toxin injection for PREvention of post-surgical PAncREatic fistula

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

27 Mar 2023 → ongoing

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Programme Hospitalier de Recherche Clinique PHRC 2017 (Ministry of Health) · MERZ France

External identifiers

EU CT number

2024-514929-33-00

EudraCT number

2018-000676-15

ClinicalTrials.gov

NCT04220931

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To study the efficacy of intrapapillary botulinum toxin injection for the prevention of postoperative pancreatic fistula (grade B and C) in the 3 months after distal pancreatectomy (DP).

Secondary objectives 13

1. To study during the 3-month postoperative follow-up the efficacy of intrapapillary botulinum toxin injection on each grade of severity of POPF (B and C)
2. To study during the 3-month postoperative follow-up the efficacy of intrapapillary botulinum toxin injection on the risk of biochemical leak (defined as a drain output with an amylase content greater than 3 times the serum amylase activity but with no clinical impact) after pancreatic surgery among patients with no pancreatic fistula
3. To study during the 3-month postoperative follow-up the efficacy of intrapapillary botulinum toxin injection on the risk of other postoperative complications: intra-abdominal fluid collection, delayed gastric emptying, post-pancreatectomy hemorrhage, pancreatitis, wound infection, other infectious complications
4. To study during the 3-month postoperative follow-up the efficacy of intrapapillary botulinum toxin injection on Clavien-Dindo classification for post-surgical morbidity
5. To study during the 3-month postoperative follow-up the efficacy of intrapapillary botulinum toxin injection on the duration of hospital stay
6. To study during the 3-month postoperative follow-up the efficacy of intrapapillary botulinum toxin injection on the risk of readmission to hospital
7. To study during the 3-month postoperative follow-up the efficacy of intrapapillary botulinum toxin injection on the risk of transfer to Intensive Care Unit and the duration of these stays
8. To study during the 3-month postoperative follow-up the efficacy of intrapapillary botulinum toxin injection on the risk of postoperative invasive procedures for the management of pancreatic fistula
9. To study during the 3-month postoperative follow-up the efficacy of intrapapillary botulinum toxin injection on the reduction of overall costs
10. To study during the 3-month postoperative follow-up the efficacy of intrapapillary botulinum toxin injection on the quality of life
11. To study during the 3-month postoperative follow-up the efficacy of intrapapillary botulinum toxin injection on the post-surgical mortality (30 and 90-day)
12. To study if BMI modify the efficacy of intrapapillary botulinum toxin injection on the prevention of postoperative pancreatic fistula (grade B and C) in the 3 months after distal pancreatectomy.
13. To study the safety of the intrapapillary botulinum toxin injection during the 3 months and 6 months postoperative follow-up.

Conditions and MedDRA coding

PANCREATIC FISTULA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Patients with scheduled distal pancreatectomy for any indication: open or minimally invasive distal pancreatectomy with or without splenectomy
2. Age ≥ 18years

Exclusion criteria 20

1. History of myasthenia gravis or Eaton-Lambert syndrome
2. Inflammatory myositis <2 years or preexisting motor neuron disease or neuropathies
3. ASA score > III
4. Pregnancy or lactation
5. Altered anatomy of the duodenum and/or the major papilla (prior surgery, prior endoscopic sphincterotomy)
6. Scheduled pancreaticoduodenectomy (Whipple procedure)
7. Scheduled total pancreatectomy
8. Scheduled central pancreatectomy
9. Scheduled pancreatic enucleation
10. Distal pancreatectomy extended to neighbouring organs (except spleen and gallbladder) or to the vessels (celiac axis, portal vein)
11. Calcified chronic pancreatitis (suspected on preoperative cross-sectional imaging)
12. Pancreas divisum (suspected on preoperative cross-sectional imaging)
13. Toxin botulinum contraindications (hypersensitivity to albumin or to saccharose, infection or inflammation at the injection site concerned, generalized muscle weakness)
14. 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
15. Any kind of surgical method to reinforce the pancreatic stump: Use of a bioabsorbable patch, Use of fibrin glue, Use of a ligament patch
16. Tutorship, trusteeship
17. Concurrent participation in other experimental trials concerning the same objective
18. Not Affiliation to the French social security
19. Not Ability to give their consent and not written informed consent
20. Secondary exclusion criteria: patients who did not have the planned surgery in less than 2 months after the botulinum toxin injection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clinically relevant POPF (grade B and C) in the 3 months after DP.

Secondary endpoints 8

1. Grade of postoperative pancreatic fistulas (B, C) based on the ISGPF 2016 update
2. Biochemical leak after surgery
3. Postoperative complications: intra-abdominal fluid collection, delayed gastric emptying, hemorrhage, pancreatitis, wound infection, other infectious complication
4. Clavien-Dindo classification for post-surgical morbidity
5. Health economics endpoints: duration of hospital stay, hospital readmissions, transfer to intensive care unit and the duration of these stays, fistularelated postoperative invasive procedures, overall costs, the incremental cost utility ratio, the incremental cost effectiveness ratio based upon the clinical endpoint of mortality and post-surgical complication including pancreatic fistula
6. Quality of life score (EQ5D5L questionnaire)
7. Postsurgical mortality (30 and 90-day)
8. Side effects related to the endoscopic botulinum toxin injection

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Frédéric PRAT

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Frédéric PRAT

Locations

1 EU/EEA country · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications