Clinical trial NCT05505006: Management of Preoperative Anaemia in Surgical Oncology
Official title: Management of Preoperative Anaemia in Surgical Oncology as a Tool to Reduce Blood Transfusion Need
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Anemia
Tumor
Keywords: anemia
surgical oncology
transfusion
patient blood management
Lead sponsor: Azienda Ospedaliera Universitaria Integrata Verona
Sponsor class: OTHER
First posted: 2022-08-17
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: * Institution of an Anemia Clinic to identify all cancer patients with anemia before surgery
* Treatment of treatable causes of anemia in all cancer patients within three weeks before surgery; in particular, iron deficiency (ID), folate deficiency and B12 deficiency
* Collection of data concerning transfusions in the peri-operative period
* Collection of peri-operative outcomes such as in-hospital mortality, myocardial infarction, ischemic stroke, acute renal failure, pneumonia, or sepsis, and Hb levels at discharge
* Comparison of data relating to transfusions and outcomes with those obtained in a historical cohort of anemic patients eligible for oncological surgery for malignant tumors, matched by age, sex, and pathology enrolled in the three years 2017-2019
* Evaluation of hepcidin levels in anemic cancer patients (explorative aim)
Primary purpose: TREATMENT

Brief summary: Preoperative anemia is detrimental in surgical patients, and its treatment with transfusions can further worsen outcomes, including increased hospital stay and mortality. Transfusions are also highly costly. In 2010, the World Health Organization endorsed the adoption of Patient Blood Management (PBM) programs, i.e., patient-centered multidisciplinary activities, including recognition and treatment of preoperative anemia. While the latter has been proved effective in reducing transfusions in setting like elective orthopedic surgery, widespread adoption is still lacking. Moreover, little is known about surgical oncology, a particular setting posing unique challenging. This change-promoting project attempts to fill this knowledge gap by establishing a multidisciplinary team aimed at optimal management of preoperative anemia in hepatobiliary/pancreas/gastrointestinal/renal surgical oncology. The primary endpoint is the reduction of transfusions, along with safer patient outcomes as compared to the historical series.

Detailed description: BACKGROUND: Preoperative anemia is frequent in patients undergoing major surgery, varying from nearly 35% in elective orthopedic surgery (EOS) to \>75% in colon cancer. Mounting data have shown that anemia is independently associated with an increased risk of morbidity and mortality in surgical patients. This is true even for mild-degree anemia, which is frequently overlooked. Of note, treatment of anemia with transfusions does not ameliorate the risk but instead appears to raise further perioperative morbidity, hospital length of stay, and mortality. Transfusions have adverse immunomodulatory effects that can increase infectious complications or cancer recurrence. Indeed, it is increasingly recognized that transfusions are one of the most costly and overused treatments in modern medicine. This has led to the implementation of Patient Blood Management (PBM) programs, i.e., patient-centered, multidisciplinary activities to promote safe and evidence-based use of transfusions. Recognition and treatment of preoperative anemia is a significant pillar of PBM, with proven efficacy in certain types of surgery, i.e., EOS. This has been facilitated by recent advances in the knowledge of the pathophysiology of iron, whose deficiency represents a common and treatable form of anemia in surgical patients. Nevertheless, evidence is scanty in surgical patients with malignancies, a particular subgroup that poses unique challenges.

Hypothesis and Significance: Recognition and treatment of preoperative anemia in surgical oncology through a well-organized, multidisciplinary Anemia Clinic should decrease blood transfusions, ultimately leading to better clinical outcomes and cost savings.

METHODOLOGIES and STATISTICAL ANALYSES: Evaluation and treatment of preoperative anemia will be performed as follows: we will perform a minimum panel of exams, i.e., complete blood count (CBC), creatinine, C-reactive protein, ferritin, transferrin saturation (TSAT), and circulating folate/B12 levels, to assess the presence of anemia, and to identify potentially correctable causes. On the same day on which the patient performs lab analyses in the morning, the surgeon will alert the Anemia Clinic with the patient's ID digital code. Case-manager MD at Anemia Clinic will evaluate lab results as soon they become available (expected time 3-4 hours after blood drawing) through the e-health system. Anemic patients will be invited to attend the Anemia Clinic the day after. They will be clinically evaluated, and treatment for anemia will be immediately prescribed/performed.

Core statistical analyses regarding transfusion use and patients' outcomes will be entrusted to external independent statisticians through subcontract. The diagnostic performance of hepcidin will be investigated through Area Under the Curve Receiving Operating Characteristic (AUC-ROC) and its prognostic implications by Kaplan-Meier curves.

The duration of the presented project is calculated as 36 months and will be divided into 3 different milestones as follows:

* M1: Study organization and coordination among the Units (study protocol preparation, procedures implementation for managing patient flow across units).
* M2: 24 months of Patient Enrolment (evaluation of preoperative hematological parameters and suitable treatment, surgery, postoperative evaluation) and ad interim follow-up evaluation after 1 month from the surgery.
* M3: statistical evaluation of results, publication preparation, and evaluation of the possible implementation of new improved internal guidelines for treating anemia in cancer patients.

Eligibility criteria: Inclusion Criteria:

* Signature of informed consent
* Eligibility to elective surgery for malignant oncological pathology.

  * Presence of pre-operative anemia (Hb \<12 g/dL females, \<13 g/dL males)
  * Age \>=18 years

Exclusion Criteria:

* Patients with chronic anemia, regularly transfused
* Patients with Hemochromatosis

Primary outcomes:
measure: Change in transfusion number compared to a historical cohort of patients enrolled in the three-year period 2017-2019
timeFrame: up to 4 weeks after surgery
measure: Change in short-term (30 days) patients' outcomes (perioperative complications including infections, cardiovascular events, and mortality) compared to a historical cohort of patients enrolled in the three years 2017-2019
timeFrame: up to 4 weeks after surgery
measure: Change in length of stay in hospital compared to a historical cohort of patients enrolled in the three-year period 2017-2019
timeFrame: up to 4 weeks after surgery
measure: Change in Hb levels (g/dl) at discharge compared to a historical cohort of patients enrolled in the three-year period 2017-2019
timeFrame: up to 4 weeks after surgery
Secondary outcomes:
Other outcomes:
measure: To evaluate the role of hepcidin in the pathophysiology of cancer-related anemia, and its potential role as prognostic parameter and in predicting the response to iron therapy
timeFrame: at patient enrollment and at hospital admission
Locations:
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata di Verona
Study officials:
References:
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