<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04438447</url>
  </required_header>
  <id_info>
    <org_study_id>RASTA-2020</org_study_id>
    <nct_id>NCT04438447</nct_id>
  </id_info>
  <brief_title>ERAS Versus ERAS Plus Artificial Nutrition in Open Pancreatoduodenectomy</brief_title>
  <acronym>RASTA</acronym>
  <official_title>ERAS Versus ERAS Plus Artificial Nutrition in Open Pancreatoduodenectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Milano Bicocca</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Milano Bicocca</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      there is a need of a randomised clinical trial specifically design to explore whether given a&#xD;
      full nutritional requirement by parenteral feeding in the first 5 days after surgery coupled&#xD;
      with oral food &quot;at will&quot; compared to only oral food &quot;at will&quot;, within an established ERAS&#xD;
      program, could achieve a reduction of the morbidity burden&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background&#xD;
&#xD;
      The enhanced recovery after surgery (ERAS) protocol is currently considered the gold-standard&#xD;
      clinical pathway for perioperative care (1). This protocol is a bundle of interventions&#xD;
      derived from the best evidence-based perioperative treatments (1). The aim of the ERAS&#xD;
      protocol is to accelerate patient recovery through the reduction of the dysmetabolic&#xD;
      consequences of surgical and anesthesiology injury. When the ERAS protocol is implemented, it&#xD;
      has been shown a reduction of the rate of surgery-related complication, length of hospital&#xD;
      stay, and health care costs (1).&#xD;
&#xD;
      The achievement of single ERAS items also facilitates a faster recovery of oral food intake&#xD;
      and of several key metabolic pathways (2). Appropriate tissue healing and&#xD;
      recovery/maintenance of organ function after an operation needs an effective and efficient&#xD;
      metabolic response, which in turn necessitates adequate qualitative and quantitative&#xD;
      nutritional substrates to be effective. Most of the evidence on the advantages of&#xD;
      implementing an ERAS program are derived from trials conducted in patients undergoing&#xD;
      colorectal surgery. In this cohort the baseline nutritional risk and the rate of malnutrition&#xD;
      is less than 10% (3). Moreover, the growing use of minimally invasive techniques has&#xD;
      facilitated a faster recovery of bowel function and optimal tolerance of early food&#xD;
      resumption after surgery (4). As a result, patients who receive a laparoscopic colorectal&#xD;
      resection easily tolerate at once the reintroduction of normal food after the operation and&#xD;
      can achieve the full nutritional requirement within 2/3 days (5).&#xD;
&#xD;
      Conversely, major pancreatic resections represent one of the most complex and challenging&#xD;
      abdominal operation that do not fit with laparoscopic approach with exception of very&#xD;
      selective cases (6). Furthermore, the proportion of patients having a high nutritional risk&#xD;
      or are malnourished at baseline is higher than 80% (7). On the top, pancreatic surgery is&#xD;
      characterized by peculiar complications such as primary delayed gastric emptying (DGE) or&#xD;
      secondary DGE after the occurrence of a pancreatic fistula. These events are frequent (up to&#xD;
      50%) (8) and deeply compromise the regular resumption of oral feeding posing patients at risk&#xD;
      of severe underfeeding. Therefore, beside the fact that early oral feeding after pancreatic&#xD;
      surgery seems safe, there are no convincing data on whether the goal of attaining adequate&#xD;
      nutritional needs is accomplished by a pure ERAS protocols (9) which endorse the use of&#xD;
      artificial nutrition only in selected cases (6). However, the level of evidence is low. In&#xD;
      fact, only one trial has specifically addressed this issue (10). In this study, the mean&#xD;
      daily calorie and protein intakes in the first 2 weeks were similar in the ERAS group and the&#xD;
      other group managed conventionally, despite the fact that during the first five&#xD;
      post-operative days, the mean daily intakes of calories and proteins slightly favored the&#xD;
      ERAS group. Overall, the authors showed that the total energy goals through oral feeding were&#xD;
      quite low in both groups.&#xD;
&#xD;
      Many of the published studies did not analyze the compliance with ERAS protocols and reported&#xD;
      incomplete data, particularly on early oral feeding (11,12). Robertson et al. (13) reported&#xD;
      compliance rates of 82% for resumption of oral fluids and 86% for tolerance of the diet.&#xD;
      Conversely, in another large trial (14), postoperative oral liquids were tolerated by 55% of&#xD;
      the patients and solid food in 53%, but compliance dropped substantially in patients with&#xD;
      major complications.&#xD;
&#xD;
      Thus, the available evidence suggests that nutritional intake using only early oral feeding&#xD;
      (food &quot;at will&quot;) within an ERAS protocol after pancreatic surgery may be only partially&#xD;
      adequate. According to expert opinions (15), artificial nutritional support should be&#xD;
      implemented early postoperatively in malnourished patients or those patients at high risk of&#xD;
      developing malnutrition, those who develop severe post-operative early after operation, and&#xD;
      in well-nourished patients who do not tolerate at least 50% of their caloric and protein&#xD;
      requirement by postoperative day 7 for any reason. Instead, other international guidelines&#xD;
      for clinical nutrition in critically ill patients (16) state that permissive underfeeding in&#xD;
      the first 3 to 7 days after hospital admission is associated with reduced morbidity and&#xD;
      mortality because excessive delivery of calories (overfeeding) may cause severe derangement&#xD;
      of several organ systems. One recent RCT, showed that in patients submitted to PD and kept&#xD;
      &quot;nil by mouth&quot; for 10 days after the operation, immediate parenteral feeding was associated&#xD;
      with less complications when compared to tube enteral nutrition (17). One systematic review&#xD;
      (18) compared the outcomes of 5 feeding routes after PD and reported no difference in terms&#xD;
      of safety and efficacy. In persisting DGE, better outcomes are achieved when artificial&#xD;
      nutrition, either parenteral or enteral, is started within 10 days of operation (19).&#xD;
&#xD;
      According to these results, there is an absence of specific evidence concerning the best&#xD;
      management of postoperative nutritional support after PD.&#xD;
&#xD;
      Given the lack of strong evidence, we believe that there is a need of a randomised clinical&#xD;
      trial specifically design to explore whether given a full nutritional requirement by&#xD;
      parenteral feeding in the first 5 days after surgery coupled with oral food &quot;at will&quot;&#xD;
      compared to only oral food &quot;at will&quot;, within an established ERAS program, could achieve a&#xD;
      reduction of the morbidity burden (20).&#xD;
&#xD;
      Study design and management&#xD;
&#xD;
      RASTA will be a randomised controlled multicentre single-blind, parallel arm, superiority,&#xD;
      phase-3 trial.&#xD;
&#xD;
      The trial will be conducted in 6 Institutions with proven experience in pancreatic surgery&#xD;
      and already applying an ERAS program (list of participating centres and principal&#xD;
      investigator of each centre in appendix 1).&#xD;
&#xD;
      Pre-trial training:&#xD;
&#xD;
      Before starting patient enrolment, a serial of meetings will be organised to accomplish:&#xD;
&#xD;
        -  Correct definition of eligibility, inclusion and exclusion criteria.&#xD;
&#xD;
        -  Accordance on definition of complications.&#xD;
&#xD;
        -  Training on randomization process and patient instruction on treatment arms.&#xD;
&#xD;
        -  Accordance on ERAS domains.&#xD;
&#xD;
        -  The training of outcome assessors will be performed to achieve concordance on the&#xD;
           occurrence of the primary and secondary endpoints. Each participating centre will&#xD;
           nominate two independent outcome assessors. In case of discordance on the assignment of&#xD;
           the endpoint, a third expert will intervene to solve the dispute and classify the&#xD;
           patients as complicated or not. Outcome assessors will be blinded to treatments&#xD;
&#xD;
        -  Training on how to fill out correctly the case report form.&#xD;
&#xD;
      Patients eligible for participation Adult patients (age ≥ 18 and &lt; 90 years of age) candidate&#xD;
      to elective pancreatoduodenectomy for any periampullary or pancreatic cancer.&#xD;
&#xD;
      Exclusion criteria:&#xD;
&#xD;
        -  American Society of Anaesthesiologists (ASA) physical status classification &gt; 3&#xD;
&#xD;
        -  Weight loss &gt; 15% with respect to usual weight in the last 6 months&#xD;
&#xD;
        -  Child-Pugh &gt; A&#xD;
&#xD;
        -  Not signed consent&#xD;
&#xD;
        -  Palliative surgery&#xD;
&#xD;
        -  Placement of a naso-enteric or jejunostomy feeding tube&#xD;
&#xD;
      Screening and randomization processes:&#xD;
&#xD;
      After being screened for inclusion and exclusion criteria, patients or their legal&#xD;
      representative will be asked to sign a written informed consent. Than subjects may be&#xD;
      enrolled in the study and randomly allocated into two arms. Randomization will be performed&#xD;
      the day before operation. All reasons for exclusion after screening will be recorded.&#xD;
&#xD;
      The study needs to be approved by the Ethical Committee of all participating centres.&#xD;
&#xD;
      The local Ethical Committee, as coordinating centre, will provide the &quot;not emendable&#xD;
      judgement&quot; according to the Italian legislation.&#xD;
&#xD;
      The trial will be registered at ClinicalTrials.gov. THE RASTA trial will be managed and&#xD;
      coordinated by the School on Medicine and Surgery of the Milano-Bicocca University at the&#xD;
      Department of Surgery of the San Gerardo Hospital, Monza, Italy. The coordinating centre will&#xD;
      be also responsible for treatment allocation and monitoring, and statistical analysis with&#xD;
      the support of the Centre of Biostatistics for Clinical Epidemiology of the Milano-Bicocca&#xD;
      University.&#xD;
&#xD;
      The expected duration of enrolment is approximately two years.&#xD;
&#xD;
      Procedures (Figure 1)&#xD;
&#xD;
      Study intervention Patients randomised in the treatment arm will be treated with a full ERAS&#xD;
      protocol that establishes oral food &quot;at will&quot; plus parenteral nutrition (PN) from&#xD;
      postoperative day 1. A 3-bag compartment peripheral parenteral solution (mOsm &lt; 800)&#xD;
      containing carbohydrate, lipids and proteins will be infused to deliver 20/25 total Kcal/kg&#xD;
      for a total of 5 days after the operation. In case of the occurrence of any complication&#xD;
      impairing the full or partial recovery of oral food, the treatment will be continued until&#xD;
      clinically indicated.&#xD;
&#xD;
      Control arm Patients randomised in the control arm will be treated with a full ERAS protocol&#xD;
      that establishes oral food &quot;at will&quot;. In case of the occurrence of any complication impairing&#xD;
      the full recovery of oral food within postoperative day 7, patients will receive parenteral&#xD;
      nutrition as in the treated arm until clinically indicated.&#xD;
&#xD;
      Procedures common to both arms Patients of both groups will be treated according to the ERAS&#xD;
      Society guidelines for perioperative care for PD (6). Attached is the ERAS guidelines for&#xD;
      pancreatic surgery. Blood glucose ≥180 mg/dL will be treated with insulin injection (either&#xD;
      subcutaneous or by continuous IV infusion)&#xD;
&#xD;
      Randomisation and masking&#xD;
&#xD;
      Patients will be randomly allocated to ERAS or ERAS plus PN at 8:00 PM of the first&#xD;
      postoperative days. Randomisation will be performed by a computed-generated permuted-block&#xD;
      sequence. A specific code will be generated for each centre to achieve equivalent grouping.&#xD;
      The allocation ratio will be 1:1 with a block size of 4. Randomization will be competitive&#xD;
      among centers.&#xD;
&#xD;
      Surgeons will not be blinded to treatment arm. Masking to allocation will be impossible to&#xD;
      achieve for the nature of the study. Patients will be evaluated for outcomes by assessors not&#xD;
      directly involved in patient care and masked to patient allocation.&#xD;
&#xD;
      Outcomes&#xD;
&#xD;
      The primary endpoint of the trial is the complication burden as measured by the Comprehensive&#xD;
      Complication Index (CCI) (20) within 30 days after hospital discharge.&#xD;
&#xD;
      Hypothesis tested - H0 hypothesis: The administration of a parenteral nutrition added to the&#xD;
      ERAS protocol will not affect the CCI as compared to standard of care (ERAS).&#xD;
&#xD;
      - H1 hypothesis: The administration of a parenteral nutrition added to the ERAS protocol will&#xD;
      affect the CCI as compared to standard of care (ERAS).&#xD;
&#xD;
      Post-discharge follow-up is accomplished by weekly outpatient visits. Also telephone&#xD;
      interviews will be allowed to monitor patient health state, but in case of warning signs or&#xD;
      symptoms of complication, the patients will be asked to refer to the hospital where the&#xD;
      operation was performed for further clinical evaluation.&#xD;
&#xD;
      Secondary outcome measures will be:&#xD;
&#xD;
        -  Daily calorie delivered by TPN&#xD;
&#xD;
        -  Rate of unplanned TPN (control group)&#xD;
&#xD;
        -  The rate and severity* of complications at 30 days after discharge.&#xD;
&#xD;
        -  Rate of surgical site infections (CDC classification) (21)&#xD;
&#xD;
        -  The rate and severity of POPF (22)&#xD;
&#xD;
        -  Rate and severity of DGE (23)&#xD;
&#xD;
        -  Rate and severity of haemorrhage (24)&#xD;
&#xD;
        -  LOS based on predefined criteria, and actual LOS&#xD;
&#xD;
        -  the rate of reoperation.&#xD;
&#xD;
        -  the rate and duration of intensive care treatment.&#xD;
&#xD;
        -  The rate of hyperglycaemia (blood glucose &gt; 180 mg/dL)&#xD;
&#xD;
        -  Use of insulin (subcutaneous bolus or continuous infusion)&#xD;
&#xD;
        -  Δ plasma prealbumin levels (baseline, POD1 and POD 6)&#xD;
&#xD;
        -  Use of morphine&#xD;
&#xD;
        -  Body weight at 30 and 90 days&#xD;
&#xD;
        -  Readmission rate&#xD;
&#xD;
        -  90-day mortality&#xD;
&#xD;
             -  The severity of complications is scored according to the Dindo-Clavien&#xD;
                classification (25) (Appendix 3).&#xD;
&#xD;
      Any attending surgeon will decide the day of discharge according to own clinical judgement.&#xD;
      However, pre-specified hospital discharge criteria will be set and recorded.&#xD;
&#xD;
      Ethical considerations&#xD;
&#xD;
      Patients in both groups will receive the best possible and most updated perioperative care&#xD;
      pathway (ERAS protocol). The experimental group will be treated with supplementary parenteral&#xD;
      nutrition to achieve the full nutritional requirement immediately after surgery. Parenteral&#xD;
      feeding is already part of the established clinical practice and in use since more than 50&#xD;
      years. The additional risk for the experimental group is to experience more episodes of&#xD;
      hyperglycaemia (blood glucose &gt; 180 mg/dL), particularly in subjects with diabetes, which&#xD;
      although will be promptly treated with insulin. Similarly, the experimental group may have an&#xD;
      additional risk of plasma electrolyte unbalance, which can be easily corrected by standard&#xD;
      treatments. In turn, as argued in the introduction section and in the hypothesis statement,&#xD;
      the experimental group might experience a reduced morbidity burden.&#xD;
&#xD;
      Safety issue&#xD;
&#xD;
      We considered as adverse events the following:&#xD;
&#xD;
        -  the number of patients not reaching tolerance to oral feeding within 7 days after&#xD;
           surgery&#xD;
&#xD;
        -  the number of patients needing insulin therapy&#xD;
&#xD;
        -  the number of patients requiring electrolyte corrections.&#xD;
&#xD;
        -  Δ Body weight (difference between baseline and discharge)&#xD;
&#xD;
      Data collection and management&#xD;
&#xD;
      All data will be collected into an electronic database with a double entry to assure&#xD;
      consistency of records. In case of missing or implausible data, queries will be mailed to the&#xD;
      participating centres to obtain integrations or corrections. Data collectors will be blinded&#xD;
      to allocation.&#xD;
&#xD;
      Statistical planning&#xD;
&#xD;
      The sample size of 120 patients per group is necessary to provide a 80% power to detect at&#xD;
      least a 30% reduction in the CCI, which is expected to be around 23 (median) (IQR 21-31) or&#xD;
      mean 27 (±20 SD) in complicated patients of the control group. The hypothesised reduction of&#xD;
      30% is based on sound clinical relevance. The median CCI of 23 is retrieved from a previous&#xD;
      publication (26). The rate of complication in this type of surgery is expected to be&#xD;
      approximately of 60%.&#xD;
&#xD;
      A Mann-Whitney test is considered, type I error rate is fixed at 5% (two tails) and an&#xD;
      expected drop-out of 10 % is taken into account.&#xD;
&#xD;
      For the binary end-points, the relative risk (RR) with the corresponding 95% confidence&#xD;
      interval, comparing the two groups, will be estimated. For the primary end-point, also the&#xD;
      risk difference (RD) will be computed. For the numerical end-points the difference in the&#xD;
      location parameter (i.e. median pairwise difference) between the two groups with the&#xD;
      corresponding 95% confidence interval will be computed. Fisher test and Mann-Whitney test&#xD;
      will be adopted to evaluate univariate associations. Incidence of complications over time in&#xD;
      the two groups will be described according to the Kaplan-Meier estimator.&#xD;
&#xD;
      A multivariate logistic regression model will be used to identify factors associated with the&#xD;
      primary endpoint and to evaluate the effect of treatment adjusting for possible residual&#xD;
      confounding. Using logistic regression, the effect of PN over controls on the CCI will be&#xD;
      also investigated within pre-specified subgroups to account for possible effect modification.&#xD;
      The pre-specified risk factors for this analysis will be:&#xD;
&#xD;
        -  NRS-2002 (≥ 3)&#xD;
&#xD;
        -  BMI (&gt; 30)&#xD;
&#xD;
        -  sex (male)&#xD;
&#xD;
        -  age (&gt; 70 years)&#xD;
&#xD;
        -  Charlson comorbidity index (&gt;4)&#xD;
&#xD;
        -  ASA score (= 3)&#xD;
&#xD;
        -  Neoadjuvant treatment&#xD;
&#xD;
        -  blood loss (≥ 500 mL)&#xD;
&#xD;
        -  Duration of surgery (&gt; 360 min)&#xD;
&#xD;
        -  Jaundice&#xD;
&#xD;
        -  Biliary stenting&#xD;
&#xD;
        -  Diabetes&#xD;
&#xD;
        -  PPPD (vs. Whipple)&#xD;
&#xD;
        -  PDAC (vs. others)&#xD;
&#xD;
        -  Fistula risk score (≥ 7)&#xD;
&#xD;
        -  ERAS overall compliance (&gt; 70%) Analyses will be done on the modified intention-to treat&#xD;
           analysis principle to represent clinical practice. All the analyses will be performed&#xD;
           with the R software.&#xD;
&#xD;
      ETHICAL / LEGAL ASPECTS:&#xD;
&#xD;
      AC / CE approval A copy of the patient's informed consent must be submitted to the CA and CE&#xD;
      together with the protocol for written approval. Written approval of the protocol and&#xD;
      informed consent must be obtained before starting the recruitment of patients in the study.&#xD;
&#xD;
      The approval of the Competent Authority (AC) / and the favorable opinion of the local Ethics&#xD;
      Committee (EC) must be obtained before the start of the experimentation.&#xD;
&#xD;
      The researcher must inform the CA and the CE of any amendments to the protocol, which must be&#xD;
      approved by both.&#xD;
&#xD;
      Informed consent The subject is considered enrolled in the study when he voluntarily provides&#xD;
      written informed consent. No study procedure will be initiated before the Informed Consent&#xD;
      has been signed. Before acquiring informed consent, the investigator explains to the subject&#xD;
      what the study consists of, what are the objectives it aims to achieve, what procedures /&#xD;
      treatments it will be necessary to carry out on the subject, any benefits for the subject,&#xD;
      such as these are the expected adverse reactions, the possibility that unexpected adverse&#xD;
      reactions may occur and any other information necessary to understand the study; the&#xD;
      explanation must take place in a manner and in a language understandable to the subject and&#xD;
      dedicating the time necessary for the subject to fully understand the study and to ask any&#xD;
      questions. Once this interview phase is over, the investigator delivers the informed Consent&#xD;
      form to the subject who can decide to sign at the moment or to take home, calmly evaluate and&#xD;
      deliver at a later time. The delivery of the form will take place at the beginning of the&#xD;
      enrollment.&#xD;
&#xD;
      Treatment of personal data The personal data object of the study must be treated in&#xD;
      compliance with the European Regulation on the Protection of Personal Data (GDPR), the&#xD;
      Legislative Decree 196/2003 and subsequent amendments and additions, and any other Italian&#xD;
      law applicable to the protection of personal data (henceforth referred to as the &quot;applicable&#xD;
      data protection law&quot;).&#xD;
&#xD;
      With regard to personal data made available to the Promoter in pseudo anonymized form, the&#xD;
      Institute and the Promoter are considered independent data controllers of the data, each for&#xD;
      its own area of competence, and both will act in compliance with the applicable data&#xD;
      protection law.&#xD;
&#xD;
      In addition, the Institute and the Promoter will cooperate to take the necessary measures in&#xD;
      order to comply with the applicable data protection law, and will also have to implement&#xD;
      appropriate technical and organizational measures to guarantee the GDPR compliance&#xD;
      requirements.&#xD;
&#xD;
      The Institute is responsible for providing its Principal Investigators and Research Staff&#xD;
      with all the necessary information relating to the methods by which the Promoter will&#xD;
      eventually collect and manage their personal data before such information is provided.&#xD;
&#xD;
      The Promoter ensures the correctness of the processing of personal data as required by the&#xD;
      GDPR. If the user becomes aware of a data breach of personal data, the user himself must&#xD;
      promptly notify the other users of this event, and in any case no later than 24 hours from&#xD;
      the knowledge of the event. In this case, the user must fully cooperate with the other users&#xD;
      to remedy the data breach, fulfilling the mandatory notification within the set times and&#xD;
      managing any damage caused.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 14, 2022</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Actual">September 10, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>RASTA will be a randomised controlled multicentre single-blind, parallel arm, superiority, phase-3 trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Patients will be randomly allocated to ERAS or ERAS plus PN at 8:00 PM of the first postoperative days. Randomisation will be performed by a computed-generated permuted-block sequence. A specific code will be generated for each centre to achieve equivalent grouping. The allocation ratio will be 1:1 with a block size of 4. Randomization will be competitive among centers.&#xD;
Surgeons will not be blinded to treatment arm. Masking to allocation will be impossible to achieve for the nature of the study. Patients will be evaluated for outcomes by assessors not directly involved in patient care and masked to patient allocation</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Comprehensive Complication Index (CCI)</measure>
    <time_frame>within 30 days after hospital discharge</time_frame>
    <description>The primary endpoint of the trial is the complication burden as measured by the Comprehensive Complication Index (CCI)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clavien-Dindo severity score</measure>
    <time_frame>30 days after discharge</time_frame>
    <description>The rate and severity of complications</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">240</enrollment>
  <condition>Pancreas Disease</condition>
  <arm_group>
    <arm_group_label>ERAS plus artificial nutrition</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomised in the treatment arm will be treated with a full ERAS protocol that establishes oral food &quot;at will&quot; plus parenteral nutrition (PN) from postoperative day 1. A 3-bag compartment peripheral parenteral solution (mOsm &lt; 800) containing carbohydrate, lipids and proteins will be infused to deliver 20/25 total Kcal/kg for a total of 5 days after the operation. In case of the occurrence of any complication impairing the full or partial recovery of oral food, the treatment will be continued until clinically indicated</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Enhanced recovery protocol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomised in the control arm will be treated with a full ERAS protocol that establishes oral food &quot;at will&quot;. In case of the occurrence of any complication impairing the full recovery of oral food within postoperative day 7, patients will receive parenteral nutrition as in the treated arm until clinically indicated</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>parenteral feeding</intervention_name>
    <description>A 3-bag compartment peripheral parenteral solution (mOsm &lt; 800) containing carbohydrate, lipids and proteins will be infused to deliver 20/25 total Kcal/kg for a total of 5 days after the operation</description>
    <arm_group_label>ERAS plus artificial nutrition</arm_group_label>
    <arm_group_label>Enhanced recovery protocol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (age ≥ 18 and &lt; 90 years of age) candidate to elective&#xD;
             pancreatoduodenectomy for any periampullary or pancreatic cancer&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  American Society of Anaesthesiologists (ASA) physical status classification &gt; 3&#xD;
&#xD;
          -  Weight loss &gt; 15% with respect to usual weight in the last 6 months&#xD;
&#xD;
          -  Child-Pugh &gt; A&#xD;
&#xD;
          -  Not signed consent&#xD;
&#xD;
          -  Palliative surgery&#xD;
&#xD;
          -  Placement of a naso-enteric or jejunostomy feeding tube&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maria G Valsecchi, PhD</last_name>
    <role>Study Director</role>
    <affiliation>University of Milano Bicocca</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Luca Gianotti, MD</last_name>
    <phone>++39-039233</phone>
    <phone_ext>9917</phone_ext>
    <email>luca.gianotti@unimib.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Silvia Mori, PhD</last_name>
    <phone>++39-02 6448</phone>
    <phone_ext>8155</phone_ext>
    <email>bicro@unimib.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Milano-Bicocca</name>
      <address>
        <city>Monza</city>
        <zip>20900</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Luca Gianotti, MD</last_name>
      <phone>++39-039233</phone>
      <phone_ext>9917</phone_ext>
      <email>luca.gianotti@unimib.it</email>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Gianotti L, Besselink MG, Sandini M, Hackert T, Conlon K, Gerritsen A, Griffin O, Fingerhut A, Probst P, Abu Hilal M, Marchegiani G, Nappo G, Zerbi A, Amodio A, Perinel J, Adham M, Raimondo M, Asbun HJ, Sato A, Takaori K, Shrikhande SV, Del Chiaro M, Bockhorn M, Izbicki JR, Dervenis C, Charnley RM, Martignoni ME, Friess H, de Pretis N, Radenkovic D, Montorsi M, Sarr MG, Vollmer CM, Frulloni L, Buchler MW, Bassi C. Nutritional support and therapy in pancreatic surgery: A position paper of the International Study Group on Pancreatic Surgery (ISGPS). Surgery. 2018 Nov;164(5):1035-1048. doi: 10.1016/j.surg.2018.05.040. Epub 2018 Jul 17.</citation>
    <PMID>30029989</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>December 1, 2022</last_update_submitted>
  <last_update_submitted_qc>December 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Milano Bicocca</investigator_affiliation>
    <investigator_full_name>Luca Vittorio Gianotti</investigator_full_name>
    <investigator_title>Professor of surgery</investigator_title>
  </responsible_party>
  <keyword>ERAS</keyword>
  <keyword>artificial nutrition</keyword>
  <keyword>pancreatoduodenectomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04438447
org study id: RASTA-2020
nct id: NCT04438447
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
there is a need of a randomised clinical trial specifically design to explore whether given a
      full nutritional requirement by parenteral feeding in the first 5 days after surgery coupled
      with oral food "at will" compared to only oral food "at will", within an established ERAS
      program, could achieve a reduction of the morbidity burden
Background

      The enhanced recovery after surgery (ERAS) protocol is currently considered the gold-standard
      clinical pathway for perioperative care (1). This protocol is a bundle of interventions
      derived from the best evidence-based perioperative treatments (1). The aim of the ERAS
      protocol is to accelerate patient recovery through the reduction of the dysmetabolic
      consequences of surgical and anesthesiology injury. When the ERAS protocol is implemented, it
      has been shown a reduction of the rate of surgery-related complication, length of hospital
      stay, and health care costs (1).

      The achievement of single ERAS items also facilitates a faster recovery of oral food intake
      and of several key metabolic pathways (2). Appropriate tissue healing and
      recovery/maintenance of organ function after an operation needs an effective and efficient
      metabolic response, which in turn necessitates adequate qualitative and quantitative
      nutritional substrates to be effective. Most of the evidence on the advantages of
      implementing an ERAS program are derived from trials conducted in patients undergoing
      colorectal surgery. In this cohort the baseline nutritional risk and the rate of malnutrition
      is less than 10% (3). Moreover, the growing use of minimally invasive techniques has
      facilitated a faster recovery of bowel function and optimal tolerance of early food
      resumption after surgery (4). As a result, patients who receive a laparoscopic colorectal
      resection easily tolerate at once the reintroduction of normal food after the operation and
      can achieve the full nutritional requirement within 2/3 days (5).

      Conversely, major pancreatic resections represent one of the most complex and challenging
      abdominal operation that do not fit with laparoscopic approach with exception of very
      selective cases (6). Furthermore, the proportion of patients having a high nutritional risk
      or are malnourished at baseline is higher than 80% (7). On the top, pancreatic surgery is
      characterized by peculiar complications such as primary delayed gastric emptying (DGE) or
      secondary DGE after the occurrence of a pancreatic fistula. These events are frequent (up to
      50%) (8) and deeply compromise the regular resumption of oral feeding posing patients at risk
      of severe underfeeding. Therefore, beside the fact that early oral feeding after pancreatic
      surgery seems safe, there are no convincing data on whether the goal of attaining adequate
      nutritional needs is accomplished by a pure ERAS protocols (9) which endorse the use of
      artificial nutrition only in selected cases (6). However, the level of evidence is low. In
      fact, only one trial has specifically addressed this issue (10). In this study, the mean
      daily calorie and protein intakes in the first 2 weeks were similar in the ERAS group and the
      other group managed conventionally, despite the fact that during the first five
      post-operative days, the mean daily intakes of calories and proteins slightly favored the
      ERAS group. Overall, the authors showed that the total energy goals through oral feeding were
      quite low in both groups.

      Many of the published studies did not analyze the compliance with ERAS protocols and reported
      incomplete data, particularly on early oral feeding (11,12). Robertson et al. (13) reported
      compliance rates of 82% for resumption of oral fluids and 86% for tolerance of the diet.
      Conversely, in another large trial (14), postoperative oral liquids were tolerated by 55% of
      the patients and solid food in 53%, but compliance dropped substantially in patients with
      major complications.

      Thus, the available evidence suggests that nutritional intake using only early oral feeding
      (food "at will") within an ERAS protocol after pancreatic surgery may be only partially
      adequate. According to expert opinions (15), artificial nutritional support should be
      implemented early postoperatively in malnourished patients or those patients at high risk of
      developing malnutrition, those who develop severe post-operative early after operation, and
      in well-nourished patients who do not tolerate at least 50% of their caloric and protein
      requirement by postoperative day 7 for any reason. Instead, other international guidelines
      for clinical nutrition in critically ill patients (16) state that permissive underfeeding in
      the first 3 to 7 days after hospital admission is associated with reduced morbidity and
      mortality because excessive delivery of calories (overfeeding) may cause severe derangement
      of several organ systems. One recent RCT, showed that in patients submitted to PD and kept
      "nil by mouth" for 10 days after the operation, immediate parenteral feeding was associated
      with less complications when compared to tube enteral nutrition (17). One systematic review
      (18) compared the outcomes of 5 feeding routes after PD and reported no difference in terms
      of safety and efficacy. In persisting DGE, better outcomes are achieved when artificial
      nutrition, either parenteral or enteral, is started within 10 days of operation (19).

      According to these results, there is an absence of specific evidence concerning the best
      management of postoperative nutritional support after PD.

      Given the lack of strong evidence, we believe that there is a need of a randomised clinical
      trial specifically design to explore whether given a full nutritional requirement by
      parenteral feeding in the first 5 days after surgery coupled with oral food "at will"
      compared to only oral food "at will", within an established ERAS program, could achieve a
      reduction of the morbidity burden (20).

      Study design and management

      RASTA will be a randomised controlled multicentre single-blind, parallel arm, superiority,
      phase-3 trial.

      The trial will be conducted in 6 Institutions with proven experience in pancreatic surgery
      and already applying an ERAS program (list of participating centres and principal
      investigator of each centre in appendix 1).

      Pre-trial training:

      Before starting patient enrolment, a serial of meetings will be organised to accomplish:

        -  Correct definition of eligibility, inclusion and exclusion criteria.

        -  Accordance on definition of complications.

        -  Training on randomization process and patient instruction on treatment arms.

        -  Accordance on ERAS domains.

        -  The training of outcome assessors will be performed to achieve concordance on the
           occurrence of the primary and secondary endpoints. Each participating centre will
           nominate two independent outcome assessors. In case of discordance on the assignment of
           the endpoint, a third expert will intervene to solve the dispute and classify the
           patients as complicated or not. Outcome assessors will be blinded to treatments

        -  Training on how to fill out correctly the case report form.

      Patients eligible for participation Adult patients (age ≥ 18 and < 90 years of age) candidate
      to elective pancreatoduodenectomy for any periampullary or pancreatic cancer.

      Exclusion criteria:

        -  American Society of Anaesthesiologists (ASA) physical status classification > 3

        -  Weight loss > 15% with respect to usual weight in the last 6 months

        -  Child-Pugh > A

        -  Not signed consent

        -  Palliative surgery

        -  Placement of a naso-enteric or jejunostomy feeding tube

      Screening and randomization processes:

      After being screened for inclusion and exclusion criteria, patients or their legal
      representative will be asked to sign a written informed consent. Than subjects may be
      enrolled in the study and randomly allocated into two arms. Randomization will be performed
      the day before operation. All reasons for exclusion after screening will be recorded.

      The study needs to be approved by the Ethical Committee of all participating centres.

      The local Ethical Committee, as coordinating centre, will provide the "not emendable
      judgement" according to the Italian legislation.

      The trial will be registered at ClinicalTrials.gov. THE RASTA trial will be managed and
      coordinated by the School on Medicine and Surgery of the Milano-Bicocca University at the
      Department of Surgery of the San Gerardo Hospital, Monza, Italy. The coordinating centre will
      be also responsible for treatment allocation and monitoring, and statistical analysis with
      the support of the Centre of Biostatistics for Clinical Epidemiology of the Milano-Bicocca
      University.

      The expected duration of enrolment is approximately two years.

      Procedures (Figure 1)

      Study intervention Patients randomised in the treatment arm will be treated with a full ERAS
      protocol that establishes oral food "at will" plus parenteral nutrition (PN) from
      postoperative day 1. A 3-bag compartment peripheral parenteral solution (mOsm < 800)
      containing carbohydrate, lipids and proteins will be infused to deliver 20/25 total Kcal/kg
      for a total of 5 days after the operation. In case of the occurrence of any complication
      impairing the full or partial recovery of oral food, the treatment will be continued until
      clinically indicated.

      Control arm Patients randomised in the control arm will be treated with a full ERAS protocol
      that establishes oral food "at will". In case of the occurrence of any complication impairing
      the full recovery of oral food within postoperative day 7, patients will receive parenteral
      nutrition as in the treated arm until clinically indicated.

      Procedures common to both arms Patients of both groups will be treated according to the ERAS
      Society guidelines for perioperative care for PD (6). Attached is the ERAS guidelines for
      pancreatic surgery. Blood glucose ≥180 mg/dL will be treated with insulin injection (either
      subcutaneous or by continuous IV infusion)

      Randomisation and masking

      Patients will be randomly allocated to ERAS or ERAS plus PN at 8:00 PM of the first
      postoperative days. Randomisation will be performed by a computed-generated permuted-block
      sequence. A specific code will be generated for each centre to achieve equivalent grouping.
      The allocation ratio will be 1:1 with a block size of 4. Randomization will be competitive
      among centers.

      Surgeons will not be blinded to treatment arm. Masking to allocation will be impossible to
      achieve for the nature of the study. Patients will be evaluated for outcomes by assessors not
      directly involved in patient care and masked to patient allocation.

      Outcomes

      The primary endpoint of the trial is the complication burden as measured by the Comprehensive
      Complication Index (CCI) (20) within 30 days after hospital discharge.

      Hypothesis tested - H0 hypothesis: The administration of a parenteral nutrition added to the
      ERAS protocol will not affect the CCI as compared to standard of care (ERAS).

      - H1 hypothesis: The administration of a parenteral nutrition added to the ERAS protocol will
      affect the CCI as compared to standard of care (ERAS).

      Post-discharge follow-up is accomplished by weekly outpatient visits. Also telephone
      interviews will be allowed to monitor patient health state, but in case of warning signs or
      symptoms of complication, the patients will be asked to refer to the hospital where the
      operation was performed for further clinical evaluation.

      Secondary outcome measures will be:

        -  Daily calorie delivered by TPN

        -  Rate of unplanned TPN (control group)

        -  The rate and severity* of complications at 30 days after discharge.

        -  Rate of surgical site infections (CDC classification) (21)

        -  The rate and severity of POPF (22)

        -  Rate and severity of DGE (23)

        -  Rate and severity of haemorrhage (24)

        -  LOS based on predefined criteria, and actual LOS

        -  the rate of reoperation.

        -  the rate and duration of intensive care treatment.

        -  The rate of hyperglycaemia (blood glucose > 180 mg/dL)

        -  Use of insulin (subcutaneous bolus or continuous infusion)

        -  Δ plasma prealbumin levels (baseline, POD1 and POD 6)

        -  Use of morphine

        -  Body weight at 30 and 90 days

        -  Readmission rate

        -  90-day mortality

             -  The severity of complications is scored according to the Dindo-Clavien
                classification (25) (Appendix 3).

      Any attending surgeon will decide the day of discharge according to own clinical judgement.
      However, pre-specified hospital discharge criteria will be set and recorded.

      Ethical considerations

      Patients in both groups will receive the best possible and most updated perioperative care
      pathway (ERAS protocol). The experimental group will be treated with supplementary parenteral
      nutrition to achieve the full nutritional requirement immediately after surgery. Parenteral
      feeding is already part of the established clinical practice and in use since more than 50
      years. The additional risk for the experimental group is to experience more episodes of
      hyperglycaemia (blood glucose > 180 mg/dL), particularly in subjects with diabetes, which
      although will be promptly treated with insulin. Similarly, the experimental group may have an
      additional risk of plasma electrolyte unbalance, which can be easily corrected by standard
      treatments. In turn, as argued in the introduction section and in the hypothesis statement,
      the experimental group might experience a reduced morbidity burden.

      Safety issue

      We considered as adverse events the following:

        -  the number of patients not reaching tolerance to oral feeding within 7 days after
           surgery

        -  the number of patients needing insulin therapy

        -  the number of patients requiring electrolyte corrections.

        -  Δ Body weight (difference between baseline and discharge)

      Data collection and management

      All data will be collected into an electronic database with a double entry to assure
      consistency of records. In case of missing or implausible data, queries will be mailed to the
      participating centres to obtain integrations or corrections. Data collectors will be blinded
      to allocation.

      Statistical planning

      The sample size of 120 patients per group is necessary to provide a 80% power to detect at
      least a 30% reduction in the CCI, which is expected to be around 23 (median) (IQR 21-31) or
      mean 27 (±20 SD) in complicated patients of the control group. The hypothesised reduction of
      30% is based on sound clinical relevance. The median CCI of 23 is retrieved from a previous
      publication (26). The rate of complication in this type of surgery is expected to be
      approximately of 60%.

      A Mann-Whitney test is considered, type I error rate is fixed at 5% (two tails) and an
      expected drop-out of 10 % is taken into account.

      For the binary end-points, the relative risk (RR) with the corresponding 95% confidence
      interval, comparing the two groups, will be estimated. For the primary end-point, also the
      risk difference (RD) will be computed. For the numerical end-points the difference in the
      location parameter (i.e. median pairwise difference) between the two groups with the
      corresponding 95% confidence interval will be computed. Fisher test and Mann-Whitney test
      will be adopted to evaluate univariate associations. Incidence of complications over time in
      the two groups will be described according to the Kaplan-Meier estimator.

      A multivariate logistic regression model will be used to identify factors associated with the
      primary endpoint and to evaluate the effect of treatment adjusting for possible residual
      confounding. Using logistic regression, the effect of PN over controls on the CCI will be
      also investigated within pre-specified subgroups to account for possible effect modification.
      The pre-specified risk factors for this analysis will be:

        -  NRS-2002 (≥ 3)

        -  BMI (> 30)

        -  sex (male)

        -  age (> 70 years)

        -  Charlson comorbidity index (>4)

        -  ASA score (= 3)

        -  Neoadjuvant treatment

        -  blood loss (≥ 500 mL)

        -  Duration of surgery (> 360 min)

        -  Jaundice

        -  Biliary stenting

        -  Diabetes

        -  PPPD (vs. Whipple)

        -  PDAC (vs. others)

        -  Fistula risk score (≥ 7)

        -  ERAS overall compliance (> 70%) Analyses will be done on the modified intention-to treat
           analysis principle to represent clinical practice. All the analyses will be performed
           with the R software.

      ETHICAL / LEGAL ASPECTS:

      AC / CE approval A copy of the patient's informed consent must be submitted to the CA and CE
      together with the protocol for written approval. Written approval of the protocol and
      informed consent must be obtained before starting the recruitment of patients in the study.

      The approval of the Competent Authority (AC) / and the favorable opinion of the local Ethics
      Committee (EC) must be obtained before the start of the experimentation.

      The researcher must inform the CA and the CE of any amendments to the protocol, which must be
      approved by both.

      Informed consent The subject is considered enrolled in the study when he voluntarily provides
      written informed consent. No study procedure will be initiated before the Informed Consent
      has been signed. Before acquiring informed consent, the investigator explains to the subject
      what the study consists of, what are the objectives it aims to achieve, what procedures /
      treatments it will be necessary to carry out on the subject, any benefits for the subject,
      such as these are the expected adverse reactions, the possibility that unexpected adverse
      reactions may occur and any other information necessary to understand the study; the
      explanation must take place in a manner and in a language understandable to the subject and
      dedicating the time necessary for the subject to fully understand the study and to ask any
      questions. Once this interview phase is over, the investigator delivers the informed Consent
      form to the subject who can decide to sign at the moment or to take home, calmly evaluate and
      deliver at a later time. The delivery of the form will take place at the beginning of the
      enrollment.

      Treatment of personal data The personal data object of the study must be treated in
      compliance with the European Regulation on the Protection of Personal Data (GDPR), the
      Legislative Decree 196/2003 and subsequent amendments and additions, and any other Italian
      law applicable to the protection of personal data (henceforth referred to as the "applicable
      data protection law").

      With regard to personal data made available to the Promoter in pseudo anonymized form, the
      Institute and the Promoter are considered independent data controllers of the data, each for
      its own area of competence, and both will act in compliance with the applicable data
      protection law.

      In addition, the Institute and the Promoter will cooperate to take the necessary measures in
      order to comply with the applicable data protection law, and will also have to implement
      appropriate technical and organizational measures to guarantee the GDPR compliance
      requirements.

      The Institute is responsible for providing its Principal Investigators and Research Staff
      with all the necessary information relating to the methods by which the Promoter will
      eventually collect and manage their personal data before such information is provided.

      The Promoter ensures the correctness of the processing of personal data as required by the
      GDPR. If the user becomes aware of a data breach of personal data, the user himself must
      promptly notify the other users of this event, and in any case no later than 24 hours from
      the knowledge of the event. In this case, the user must fully cooperate with the other users
      to remedy the data breach, fulfilling the mandatory notification within the set times and
      managing any damage caused.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: RASTA will be a randomised controlled multicentre single-blind, parallel arm, superiority, phase-3 trial
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Patients will be randomly allocated to ERAS or ERAS plus PN at 8:00 PM of the first postoperative days. Randomisation will be performed by a computed-generated permuted-block sequence. A specific code will be generated for each centre to achieve equivalent grouping. The allocation ratio will be 1:1 with a block size of 4. Randomization will be competitive among centers.
Surgeons will not be blinded to treatment arm. Masking to allocation will be impossible to achieve for the nature of the study. Patients will be evaluated for outcomes by assessors not directly involved in patient care and masked to patient allocation
measure: Comprehensive Complication Index (CCI)
time frame: within 30 days after hospital discharge
description: The primary endpoint of the trial is the complication burden as measured by the Comprehensive Complication Index (CCI)
measure: Clavien-Dindo severity score
time frame: 30 days after discharge
description: The rate and severity of complications
arm group label: ERAS plus artificial nutrition
arm group type: Experimental
description: Patients randomised in the treatment arm will be treated with a full ERAS protocol that establishes oral food "at will" plus parenteral nutrition (PN) from postoperative day 1. A 3-bag compartment peripheral parenteral solution (mOsm < 800) containing carbohydrate, lipids and proteins will be infused to deliver 20/25 total Kcal/kg for a total of 5 days after the operation. In case of the occurrence of any complication impairing the full or partial recovery of oral food, the treatment will be continued until clinically indicated
arm group label: Enhanced recovery protocol
arm group type: Active Comparator
description: Patients randomised in the control arm will be treated with a full ERAS protocol that establishes oral food "at will". In case of the occurrence of any complication impairing the full recovery of oral food within postoperative day 7, patients will receive parenteral nutrition as in the treated arm until clinically indicated
intervention type: Dietary Supplement
intervention name: parenteral feeding
description: A 3-bag compartment peripheral parenteral solution (mOsm < 800) containing carbohydrate, lipids and proteins will be infused to deliver 20/25 total Kcal/kg for a total of 5 days after the operation
arm group label: ERAS plus artificial nutrition
arm group label: Enhanced recovery protocol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Maria G Valsecchi, PhD
role: Study Director
affiliation: University of Milano Bicocca
last name: Luca Gianotti, MD
phone: ++39-039233
phone ext: 9917
email: luca.gianotti@unimib.it
last name: Silvia Mori, PhD
phone: ++39-02 6448
phone ext: 8155
email: bicro@unimib.it
facility: 
status: Recruiting
contact: 
country: Italy
citation: Gianotti L, Besselink MG, Sandini M, Hackert T, Conlon K, Gerritsen A, Griffin O, Fingerhut A, Probst P, Abu Hilal M, Marchegiani G, Nappo G, Zerbi A, Amodio A, Perinel J, Adham M, Raimondo M, Asbun HJ, Sato A, Takaori K, Shrikhande SV, Del Chiaro M, Bockhorn M, Izbicki JR, Dervenis C, Charnley RM, Martignoni ME, Friess H, de Pretis N, Radenkovic D, Montorsi M, Sarr MG, Vollmer CM, Frulloni L, Buchler MW, Bassi C. Nutritional support and therapy in pancreatic surgery: A position paper of the International Study Group on Pancreatic Surgery (ISGPS). Surgery. 2018 Nov;164(5):1035-1048. doi: 10.1016/j.surg.2018.05.040. Epub 2018 Jul 17.
PMID: 30029989
responsible party type: Principal Investigator
investigator affiliation: University of Milano Bicocca
investigator full name: Luca Vittorio Gianotti
investigator title: Professor of surgery
mesh term: Pancreatic Diseases
sharing ipd: No