The aim of DIPLOMA-2 is to compare MIPD with OPD regarding post-operative complications (non-inferiority) and time to functional recovery (superiority) for pancreatic and peri-ampullary neoplasm in high-volume centers in an enhanced recovery setting…
ID
Source
Brief title
Condition
- Other condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal therapeutic procedures
Synonym
Health condition
(pre)maligne pancreas- en/of periampullaire tumoren
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome is CCI® (Comprehensive Complication Index), measuring all
complications up to 90 days after surgery, all scored according to the
Clavien-Dindo classification:
Grade I:
Any deviation from the normal postoperative course without the need for
pharmacological treatment or surgical, endoscopic and radiological
interventions. Allowed therapeutic regimens are: drugs as antiemetics,
antipyretics, analgetics, diuretics and electrolytes and physiotherapy. This
grade also includes wound infections opened at the bedside.
Grade II:
Requiring pharmacological treatment with drugs other than such allowed for
grade I complications.
Blood transfusionsand total parenteral nutritionare also included.
Grade III:
Requiring surgical, endoscopic or radiological intervention
- IIIa
Intervention not under general anesthesia
- IIIb
Intervention under general anesthesia
Grade IV:
Life-threatening complication (including CNS complications)* requiring
IC/ICU-management
- IVa
single organ dysfunction (including dialysis)
- IVb
multiorgandysfunction
Grade V Death of a patient.
The CCI score is a cumulative representation of all post-operative
complications, in a score from 0 (no complications) to 100 (worst outcome =
death of patient).
For the second study phase (DIPLOMA-2x2) the primary endpoint is the
microscopically radical resection margin (R0, distance tumor to pancreatic
transection and posterior margin >= 1 mm), which is assessed using a Royal
College of Pathologists criteria. This histopathological assessment includes
both the transection and posterior margins (surgical margins), but excludes
theand the anterior and superior/inferior margins/surface (anatomical margins).
In order to ensure uniformity, study coordinators will be present in all
centers during surgery of the first patient and subsequent handling of the
specimen by the pathologist. Pathologists will be asked to report the
individual margins/surfaces. A secondary analysis will include only the
*surgical margins* (pancreas, superior mesenteric artery, bile duct,
stomach/small bowel). Also, a validation will be performed by reviewing 10% of
specimens by external pathologists. Involved pathologists will be blinded for
the applied surgical approach.
Secondary outcome
The most relevant secondary endpoint is the time to functional recovery in
days.
Other secondary endpoints are:
- Operative parameters (operative time, blood loss, blood transfusion,
conversion)
- Postoperative parameters (complications, mortality, re-interventions,
activity (measured by activity tracker)
- Other pathology parameters (tumor size, lymph node resection, number of
positive glands, invasion, grading and staging)
- Hospitalization parameters (total length of hospital stay, readmission,
intensive care admission)
- Oncologic parameters (use of (neo-)adjuvant chemotherapy, 3-year survival,
disease-free survival)
- Quality of life
- Cost of care
Background summary
For patients with a (pre-)malignant pancreatic or periampullary tumor, the
pancreatoduodenctomy (Whipple) is the only treatment with curative intent.
Pancreatoduodenectomy is a complex operation with a high risk of complications
and is therefore reserved for specialized centers and experienced surgeons. The
minimally invasive approach for pancreatoduodenectomy (MIPD) is slowly becoming
part of clinical practice and several successful training programs have already
been established. In previous studies in high-volume centers, MIPD has been
associated with benefits such as shorter admission duration, less blood loss
and comparable mortality to open pancreatoduodenectomy (OPD). However, MIPD is
associated with higher intraoperative costs and longer learning curve, and the
current literature shows conflicting results with regard to post-operative
complications. A multicenter randomized trial in expertise centers is therefore
essential to compare the safety and benefits of MIPD (both robotic and
laparoscopic) with OPD for pancreatic and peri-ampullary tumors.
Study objective
The aim of DIPLOMA-2 is to compare MIPD with OPD regarding post-operative
complications (non-inferiority) and time to functional recovery (superiority)
for pancreatic and peri-ampullary neoplasm in high-volume centers in an
enhanced recovery setting.
Study design
An international multicenter randomized controlled patient-blinded trial. The
study will be conducted in centers with a minimum annual volume of 30 MIPDs and
surgeons with a personal experience of at least 60 MIPDs. A blinded
adjudication committee will assess all endpoints. The protocol is designed
according to the SPIRIT guidelines.1
Intervention
Minimally invasive (laparoscopic or robot-assisted) pancreatoduodenectomy
Study burden and risks
Recent comparative studies and three randomized controlled trials (RCT)
conducted in high-volume centers suggest that laparoscopic
pancreatoduodenectomy (LPD) is superior to open pancreatoduodenectomy (OPD) in
terms of intra-operative blood loss and length of hospital stay. However,
outcomes on complications of LPD in literature are conflicting, though
influenced by patient-allocation bias. No RCTs on robot-assisted
pancreatoduodenectomy have been conducted yet, but retrospective studies from
high-volume centers have shown the safety and feasibility and several RPD
training programs have been succesfully conducted. Trials assessing the time to
functional recovery and oncologic safety of minimally invasive
pancreatoduodenectomy (MIPD; LPD and RPD) are lacking. Wordwide, both LPD and
RPD are now part of normal clinical practice in expertise centers. The subjects
will not undergo additional investigations and interventions in the DIPLOMA-2
trial and therefore risks within the study will be similar to the risks of
normal clinical practice. Potential benefits for subjects undergoing MIPD may
include: less blood loss, better ability to endure complications, faster
functional recovery, shorter hospital stay, and better cosmetics.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
• Age at least 18 years;
• Indication for elective pancreatoduodenectomy for a tumor located in the
pancreatic head, distal bile duct, duodenum or ampulla of Vater; in the second
phase of the study (after 288 patients are included) only patients with a
malignant tumor of the pancreatic head or distal bile duct will be eligible for
inclusion
• Both minimally invasive pancreatoduodenectomy and open pancreatoduodenectomy
are technically feasible for radical resection, according to the local
treatment team;
• Pre-operative multiphase CT scan showing no signs of vascular involvement (3D
reconstruction optional).
o In case of (suspected) malignancy: maximum 28 days old CT-scan available.
• Fit to undergo pancreatoduodenectomy according to the surgeon and
anesthesiologist
• Written informed consent
Exclusion criteria
- A second cancer requiring resection during the same procedure - Chronic
pancreatitis as indication (including Groove pancreatitis) - Any vascular
involvement (portal vein, superior mesenteric vein, superior mesenteric artery,
coeliac artery or hepatic artery) - Pregnancy - Body mass index >35 kg/m2 -
Participation in another study with interference of study outcomes - Not able
or willing to complete the (quality-of-life) questionnaires Hybrid procedures
in which the resection is performed via a laparoscopic approach and the
reconstruction via an open approach are not allowed in this study.
Design
Recruitment
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ISRCTN | ISRCTN27483786 |
| CCMO | NL77750.018.21 |