Management of Preoperative Anaemia in Surgical Oncology

August 17, 2022 updated by: Fabiana Busti, Azienda Ospedaliera Universitaria Integrata Verona

Management of Preoperative Anaemia in Surgical Oncology as a Tool to Reduce Blood Transfusion Need

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

500

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Verona, Italy, 37134
        • Recruiting
        • Azienda Ospedaliera Universitaria Integrata di Verona
        • Contact:
        • Principal Investigator:
          • Domenico Girelli, Prof.
        • Sub-Investigator:
          • Alfredo Guglielmi, Prof.
        • Sub-Investigator:
          • Giorgio Gandini, MD
        • Sub-Investigator:
          • Giovanni Marchegiani, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cancer patients with anemia (i.e. Hb <12 g/dl if females, <13 g/dL if males)

Cancer patients eligible for surgery with anemia will be managed as follows:

  • s-ferritin <100 mcg/l or s-ferritin <500 mcg/l + TSAT<20% = i.v. iron (ferric carboxymaltose, dosage according to body weight and Hb level)
  • folate < 5 ng/ml = folate 5 mg per day for 1 month
  • B12 < 200 pg/ml = B vitamin complex 1 tablet per day for 1 month

Patients will receive combined treatment if they have multiple deficiencies simultaneously.

Patients without correctable deficiencies will not receive any treatment.
Drug: Ferric Carboxymaltose Injection
Anemic patients with ID will receive i.v. iron. Dosage will be based on Hb level and patient body weight.
Other Names:
  • i.v. iron
Drug: Folic acid
Anemic patients with folate deficiency will receive folic acid 5 mg per day for 1 month
Other Names:
  • Folate
Drug: B12
Anemic patients with B12 deficiency will receive B vitamin complex 1 tablet per day for 1 month
Other Names:
  • cobalamin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in transfusion number compared to a historical cohort of patients enrolled in the three-year period 2017-2019
Time Frame: up to 4 weeks after surgery
Evaluate whether implementing a program for early recognition and management of preoperative anemia leads to a reduction in blood transfusions in surgical oncology compared to historical cohort enrolled before the project
up to 4 weeks after surgery
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
Time Frame: up to 4 weeks after surgery
Evaluate whether implementing a program for early recognition and management of preoperative anemia leads to an improvement in some patient's clinical outcomes after surgery compared to the historical cohort enrolled before the project
up to 4 weeks after surgery
Change in length of stay in hospital compared to a historical cohort of patients enrolled in the three-year period 2017-2019
Time Frame: up to 4 weeks after surgery
Evaluate whether implementing a program for early recognition and management of preoperative anemia leads to a shortening in the duration of hospitalization after surgery compared to the historical cohort enrolled before the project
up to 4 weeks after surgery
Change in Hb levels (g/dl) at discharge compared to a historical cohort of patients enrolled in the three-year period 2017-2019
Time Frame: up to 4 weeks after surgery
Evaluate whether implementing a program for early recognition and management of preoperative anemia leads to an improvement in Hb levels at discharge compared to the historical cohort enrolled before the project
up to 4 weeks after surgery

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: at patient enrollment and at hospital admission
hepcidin levels
at patient enrollment and at hospital admission

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliera Universitaria Integrata Verona

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2021

Primary Completion (Anticipated)

August 13, 2024

Study Completion (Anticipated)

August 13, 2024

Study Registration Dates

First Submitted

August 11, 2022

First Submitted That Met QC Criteria

August 16, 2022

First Posted (Actual)

August 17, 2022

Study Record Updates

Last Update Posted (Actual)

August 19, 2022

Last Update Submitted That Met QC Criteria

August 17, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CO-2016-02361206

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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