Condition category
Surgery
Date applied
18/02/2019
Date assigned
18/02/2019
Last edited
22/03/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Patients with benign lesions of the left part of the pancreas often need resection of the left part of the pancreas, a distal pancreatectomy (DP). DP often involves removal of the spleen because the blood supply of the spleen is close or adherent to the pancreas. Patients without a spleen have an increased risk of developing possibly lethal infectious complications, thrombosis, as well as certain cancers. Because of the risk of infectious complications, patients require regular vaccinations and a lifelong course of antibiotics. Because of these risks, spleen-preserving DP is now the preferred approach. However, splenic preservation is not always technically feasible and many patients end up with their spleen resected (splenectomy). In this study the researchers will reimplant pieces of the resected spleen (autogenic splenic implantation) at the same operation and assess the immunological function of these transplanted pieces of spleen.

Who can participate?
Adults who require distal pancreatectomy for a benign or premalignant lesion

What does the study involve?
Undergoing distal pancreatectomy as part of standard of care. Additionally, in case splenectomy is performed, participants are randomly allocated to undergo just splenectomy or to receive splenic transplants (autogenic splenic implantation). Six months after reimplantation, the participants are vaccinated with a Salmonella vaccine to test the immune response of the body to this vaccine by measuring antibodies in the blood. Antibodies are produced by the immune system and help clear the body from infections. The antibody response of participants who underwent autogenic splenic implantation is compared with participants who underwent spleen preserving DP and participants who underwent DP with splenectomy. If the antibody response is adequate, patients may no longer require regular vaccinations and lifelong antibiotics in the future.

What are the possible benefits and risks of participating?
Participants potentially get back their splenic function if the spleen is removed and the new pieces of spleen are transplanted back in the abdomen. This could potentially prevent the increased risk of infectious complications after removal of the spleen. No other treatments exist to restore the function of the spleen after its removal. Participants are at risk of developing the known complications of pancreatic surgery but these are the same in patients who do not participate. Previous research has shown there are very few additional complications in patients who underwent transplantation of pieces of their own spleen. Very rarely one of the pieces does not survive and can get infected and become an abscess. In addition, two cases of bowel obstruction have occurred in the past that could have been related to the transplanted pieces of spleen. A possible risk of the vaccine is local pain after the injection, in most cases this resolves in 24 – 48 hours. Another possible risk is an allergic reaction to the vaccine.

Where is the study run from?
University Hospital Southampton NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
June 2018 to April 2022

Who is funding the study?
NIHR and the Liver & Pancreatic Cancer Charity (UK)

Who is the main contact?
Dr AL Moekotte
a.l.moekotte@soton.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Alma Moekotte

ORCID ID

http://orcid.org/0000-0002-2883-4483

Contact details

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

39052

Study information

Scientific title

Autogenic splenic implantation in distal pancreatectomy with splenectomy for benign lesions of the distal pancreas

Acronym

RESTORE trial version 1

Study hypothesis

The hypothesis of this study is that autogenic splenic implantation after distal pancreatectomy and splenectomy for benign lesions is safe and feasible and will restore the immunological function of the spleen.

Ethics approval

South Central – Hampshire B Research Ethics Committee, Level 3 Block B, Whitefriars, Lewins Mead, Bristol, BS1 2NT, Tel: +44 (0)207 1048055, Email: nrescommittee.southcentral-hampshireb@nhs.net, 16/08/2018, ref: 248540

Study design

Randomised; Interventional; Design type: Treatment, Surgery

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Autogenic splenic implantation to prevent hyposplenism following distal pancreatectomy for benign neoplasm of the pancreas

Intervention

All patients are discussed in a multi-disciplinary team (MDT) meeting where the surgical approach will be determined, either distal pancreatectomy with splenectomy (DPS) or spleen-preserving distal pancreatectomy (SPDP). If the determined approach is DPS, patients will be randomised preoperatively to either DPS or DPS with autogenic splenic implantation (ASI). If SPDP is the preferred approach, splenectomy will only be performed if splenic preservation cannot be achieved due to technical or safety reasons during the operation. In case splenectomy is inevitable, intraoperative randomising will be performed to either DPS or DPS with ASI. Three groups will be formed:
1. ASI
2. DPS
3. SPDP
Patients will be randomised between ASI and DPS in a 1:1 ratio. An online randomisation system performing variable block randomisation will be used.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

Immunologic splenic function assessed using levels of Salmonella typhi specific antibodies (Ab) prior to and after vaccination with the Typhim Vi™ polysaccharide vaccine. The levels of Salmonella typhi specific of Ab raised in response to the Typhim Vi™ polysaccharide vaccine will be measured by using the Salmonella typhi Vi IgG ELISA Assay. Pre-vaccination levels will be measured at 6 months postoperatively and post-vaccination levels at 7 months postoperatively.

Secondary outcome measures

1. 30-day mortality, described as mortality during initial hospitalisation or within 30 days postoperative, measured daily as long as participant is in hospital, thereafter at 2 weeks and 6 weeks after discharge
2. 30-day postoperative complication rate, the occurrence of any postoperative complication, measured daily as long as participant is in hospital, thereafter at 2 weeks and 6 weeks after discharge
3. Hospital stay, described as number of postoperative days in hospital, measured once after discharge
4. Operating time, described as number of minutes from incision to closure of skin, measured once after the operation
5. Estimated blood loss, described as the estimated blood loss during the operation, measured once after the operation
6. Blood transfusion required, described as any blood transfusion given during the operation of after during initial hospitalisation, measured once after discharge

Overall trial start date

05/06/2018

Overall trial end date

01/04/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Adults
2. Indication for distal pancreatectomy for suspected benign lesion
3. Either spleen-preserving or with splenectomy
4. Either open or laparoscopic
5. Fit to undergo distal pancreatectomy (American Society of Anaesthesiologist classification of 3 or below)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 45; UK Sample Size: 45

Participant exclusion criteria

1. Proven or suspected malignant lesion of the pancreatic body or tail
2. Asplenia, either functional, surgical or congenital
3. Any other known immune deficiency disorder
4. Known allergy to any of the Typhim Vi vaccine containing components
5. Pregnancy
6. Unfit to undergo distal pancreatectomy (American Society of Anaesthesiologist classification above 3)
7. Prisoners and adults lacking capacity to consent

Recruitment start date

01/10/2018

Recruitment end date

01/04/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University Hospital Southampton NHS Foundation Trust (lead centre)
Tremona Road
Southampton
SO16 6YD
United Kingdom

Sponsor information

Organisation

University Hospital Southampton NHS Foundation Trust

Sponsor details

Mailpoint 18
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
+44 (0)2381208689
mikayala.king@uhs.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

NIHR Central Commissioning Facility (CCF); Grant Codes: NF-SI-0515-10059,

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

University Hospital Southampton NHS Foundation Trust

Alternative name(s)

Funding Body Type

government organisation

Funding Body Subtype

Local government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Protocol will be published at a later stage. Planned publication of the results in a high-impact peer reviewed journal.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/04/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

22/03/2019: The condition has been changed from "Specialty: Surgery, Primary sub-specialty: General Surgery; Health Category: Cancer and neoplasms, Inflammatory and immune system; Disease/Condition: Certain disorders involving the immune mechanism, Benign neoplasms" to "Autogenic splenic implantation to prevent hyposplenism following distal pancreatectomy for benign neoplasm of the pancreas" following a request from the NIHR. The condition category has been changed from "Cancer" to "Surgery". 18/02/2019: Trial's existence confirmed by the NIHR.