Clinical trial NCT06981273: Robotic vs Open Pancreatoduodenectomy
Official title: SPAIN Trial Comparing Open vs Robotic Pancreatoduodenectomy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Pancreas Neoplasms
Keywords: Robotic
pancreaticoduodenectony
Robotic surgery
Lead sponsor: Hospital del Mar
Sponsor class: OTHER
First posted: 2025-05-20
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pancreatic surgery, specifically pancreatoduodenectomy (PD), is a complex procedure often required for patients with pancreatic or other periampullary cancers. In recent years, minimally invasive techniques have become more popular, especially robotic-assisted surgery. However, there are limited studies comparing robotic surgery to traditional open surgery.

This is a national, multicenter study in Spain comparing the outcomes of robotic versus open pancreatoduodenectomy (PD). The main goal is to assess complications within 90 days after surgery. This study is important because it will provide evidence on which approach is safer and more effective for patients.

The study follows a \*\*prospective, randomized, and multicenter design\*\*, meaning patients are assigned to either robotic or open surgery randomly, and multiple hospitals are involved. The study will include all eligible patients undergoing planned PD surgery, either by robotic or open technique.

To be included in the study, patients must meet these conditions:

* Be \*\*18 years or older\*\*.
* Require \*\*planned PD surgery\*\*.
* Sign an \*\*informed consent form\*\*.

Who Cannot Participate?

Patients will \*\*not\*\* be included if they:

* \*\*Refuse the procedure\*\*.
* Have \*\*uncertainty about vascular involvement\*\*.
* Have a severe health condition classified as \*\*ASA IV\*\* (high-risk for surgery).

The main outcome measured will be the \*\*Comprehensive Complication Index (CCI), a standardized way to assess post-surgical complications. Additional factors being studied include:

* \*\*Clinical outcomes\*\* during and after surgery.
* \*\*Quality of life\*\* assessments.
* \*\*Surgical costs\*\*.
* \*\*Hospital stay duration\*\*.
* \*\*Need to switch from robotic to open surgery\*\*.
* \*\*Need for additional surgery (reoperations)\*\*.
* \*\*Hospital readmissions\*\*.

Where Is the Study Being Conducted?

The study is being conducted in \*\*ten major hospitals across Spain\*\*:

1. Hospital del Mar, Barcelona
2. Hospital Balmis, Alicante
3. Hospital Vall d'Hebron, Barcelona
4. Arnau de Vilanova, Lleida
5. Joan XXIII, Tarragona
6. Hospital Sant Pau, Barcelona
7. Germans Trias i Pujol, Barcelona
8. Hospital Clínic, Barcelona
9. HM Sanchinarro, Madrid
10. Hospital Rio Hortega, Valladolid

How Long Will the Study Last? The study will take \*\*two years\*\* to complete, and patients will be followed for \*\*three years\*\* after surgery to track long-term outcomes.

Why Is This Study Important for Patients? For patients undergoing PD, this study will provide essential information about the risks and benefits of robotic versus open surgery. The findings will help doctors determine the best surgical approach, leading to improved safety, faster recovery, and better long-term health outcomes.

If you are a patient facing this type of surgery, participating in this study could contribute to valuable medical knowledge while ensuring that you receive a carefully monitored treatment plan.

Detailed description: Introduction

Pancreatoduodenectomy (PD), commonly known as the Whipple procedure, is a complex surgical procedure used to treat pancreatic, bile duct, and duodenal diseases, including cancer. Traditionally, this surgery has been performed using an open approach (PDA), but recent advancements in minimally invasive techniques have introduced the robotic approach (PDR) as a potential alternative.

Minimally invasive robotic surgery may offer benefits such as reduced blood loss, shorter hospital stays, and potentially lower complication rates. However, there is limited high-quality evidence comparing the outcomes of robotic PD versus open PD. This national, multicenter, randomized clinical trial aims to provide clear answers by analyzing postoperative complications and overall patient outcomes.

Primary Objective

Evaluate postoperative complications using the CCI within 90 days after surgery.

Objectives This clinical trial aims to compare two different surgical approaches, PDR and PDA, in relation to postoperative morbidity within 90 days following surgery. Morbidity is assessed using the Complication Index (CCI) (www.assesssurgery.com). The primary objective is to measure CCI®, which tracks complications up to 90 days after surgery. Secondary objectives include intraoperative variables (e.g., blood loss, operative time, and conversion), postoperative morbidity (e.g., pancreatic-specific complications as defined by ISGPS), oncological outcomes in cases of malignancy (radicality, lymph node removal, and time until adjuvant chemotherapy), healthcare resource utilization (length of stay, readmissions, ICU stay), and quality of life and recovery post-surgery.

Secondary Objectives

Intraoperative outcomes: Blood loss, operative time, and conversion rates from robotic to open surgery.

Postoperative morbidity: Evaluated using the International Study Group of Pancreatic Surgery (ISGPS) definitions.

Oncological outcomes (for cancer patients): Tumor clearance, number of lymph nodes removed, and time to adjuvant chemotherapy.

Healthcare resource utilization: Hospital stay, ICU admission, and hospital readmissions.

Quality of life and recovery after surgery.

Hypothesis The PDR surgical procedure demonstrates non-inferiority in the post-operative CCI score up to 90 days after surgery.

Materials and Methods

Study Design

This is a national, multicenter, randomized, prospective clinical trial with parallel groups comparing patients undergoing PD for any cause. Patients will be randomized into two groups:

Group 1: PDR Group 2: PDA The study will span 2 years. The research will be conducted in centers with an annual volume of at least 30 pancreatic resections (distal and cephalic) and surgeons with personal experience of at least 20 PDRs annually. A minimum of 30 pancreatic resections includes at least 20 pancreatoduodenectomies annually.

Sample Size This is a non-inferiority study. According to previous studies, a clinically relevant mean difference in CCI is 7.5, while the average standard deviation is approximately 20 in major abdominal surgeries. A total of 93 patients will need to be enrolled in the trial (46 and 47 per group), accounting for a 5% dropout rate, with an alpha error of 5% and a beta error of 20%.

Data Collection

Clinical Data Postoperative complications will be classified and evaluated according to the Clavien-Dindo classification (I to V) and the CCI numeric scale (www.assesssurgery.com). Major complications are those rated IIIa or higher. Complications, readmissions, and mortality will be measured up to 90 days.

Safety Assessment of Procedures

Both techniques, PDR and PDA, will be evaluated for adverse events. The following complications will be recorded in the Clinical Data Record (CRD):

Blood loss and need for transfusion during the procedure Postoperative hemorrhage Postoperative transfusion Biliary fistula Need for re-intervention Need for readmission Postoperative death Economic Data Economic data will be collected based on the single cost assigned to each procedure, calculated using the RECH system (Spanish Hospital Cost Network: https://www.rechosp.org). The costs will be derived from the National Health System's (SNS) diagnostic-related groups (DRG). The total cost will be calculated by multiplying the number of resource units used by the unit cost.

Measures to Minimize Bias Two main limitations are anticipated. The first concerns variability in surgical techniques among the surgeons. To minimize this, a meeting of all participating centers will be held to standardize surgical techniques. Furthermore, quality control will involve sending a video of the PDR procedure from each surgeon for evaluation.

The second limitation relates to patient recruitment. To address this, a conservative estimate of potential candidates was made, and centers with high volumes of pancreatic resections (at least 30 per year, including 20 pancreatoduodenectomies) have been selected.

Randomization Randomization will be performed using block assignment stratified by center, ensuring balanced groups within each participating hospital. Randomization between the robotic and open arms will occur before surgery with a 1:1 ratio using an online system.

Blinding This study will be single-blinded, meaning patients will not be aware of which group they belong to. After surgery, a cover will be applied to the abdominal wall so patients cannot see whether they had a robotic or open procedure.

Surgical Procedures

PDA:

The procedure begins with a bilateral subcostal incision. After initial exploration, if no distant disease is found, a PD will be performed. Reconstruction follows after the surgical specimen is removed.

PDR:

The procedure starts with robotic trocar placement, along with up to two additional laparoscopic trocars. Surgical steps follow the PDA procedure, but the specimen is removed through a mini-incision. Hybrid techniques (laparoscopic resection and robotic reconstruction) are excluded.

Data Recording Study variables will be stored in an online data collection form (CRD), which will automatically transfer data to a database. The system used for this will be Red Cap. The investigators and study monitor will have digital access to the Red Cap database to include new patients and review data during follow-up. Patient names will not appear in the database to ensure confidentiality. A subject code will be used for anonymity, and an identification register will link the code to the patient's medical record.

Statistical Analysis Data will be analyzed using IBM SPSS Statistics for Windows version 24.0 (IBM Corp.). Statistical tests such as Student's T-test, Mann-Whitney U test, Chi-square, and Fisher's exact test will be employed. Categorical data will be presented as frequency and percentage, and continuous data as mean, standard deviation, or median with interquartile range. Subgroups will be analyzed using Chi-square, Mann-Whitney U, and Kruskal-Wallis tests, with p\<0.05 indicating statistical significance.

Ethical Aspects The study will be registered on www.controlled-trials.com and will follow the ethical principles of the Declaration of Helsinki (2013) and Good Clinical Practice (GCP). Informed consent will be obtained from all participants, and the study will be reviewed by an Ethics Committee. The protocol will be registered on clinicaltrial.gov. Confidentiality will be maintained, and data will not be shared with third parties without consent.

Sample Management and Confidentiality Only necessary biological samples will be taken, with all patient data stored pseudonymized to ensure confidentiality. The study will comply with GDPR and local privacy laws.

Funding Funding for the study will be requested from the Spanish Association of Surgeons (AEC) for a total of €10,000, which will be used for insurance and monitoring.

Monitoring and Auditing The study will be monitored by clinical investigators and a data manager for periodic center audits.

Public Disclosure and Publication Results will be submitted to a high-impact medical journal, with authorship based on participant center recruitment volume. The study's findings will also be published in scientific journals following local regulations.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older.
* Patients requiring planned pancreatoduodenectomy (robotic or open).
* Signed informed consent to participate in the study.

Exclusion Criteria:

* Patients who refuse the procedure.
* Uncertainty about vascular involvement that could affect resectability.
* Poor general health status (American Society of Anesthesiologists \[ASA\] classification IV).
* Pancreatitis

Primary outcomes:
measure: Complication Index
timeFrame: up to 90 days after surgery
Secondary outcomes:
measure: Cost effectiveness
timeFrame: 3 months after surgery
measure: Tumor clearance
timeFrame: until the end of the study
measure: operative time
timeFrame: during the surgery
measure: Blood loss
timeFrame: during the surgery
measure: Conversion to open surgery
timeFrame: during surgery
measure: Pancreatic Fistula
timeFrame: after surgery up to 90 days from operation
measure: EORTC QLQ-C30
timeFrame: before and after surgery at 30 and 90 days
measure: QoR-15
timeFrame: after surgery at 30 and 90 days
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital del Mar
Study officials:
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