Management of Preoperative Anaemia in Surgical Oncology

NCT ID: NCT05505006

Last Updated: 2022-08-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-02
• Study Completion Date: 2024-08-13

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.

Conditions

Anemia; Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ferric Carboxymaltose Injection

Intervention Type: DRUG

Anemic patients with ID will receive i.v. iron. Dosage will be based on Hb level and patient body weight.

Folic acid

Intervention Type: DRUG

Anemic patients with folate deficiency will receive folic acid 5 mg per day for 1 month

B12

Intervention Type: DRUG

Anemic patients with B12 deficiency will receive B vitamin complex 1 tablet per day for 1 month

Interventions

Ferric Carboxymaltose Injection

Anemic patients with ID will receive i.v. iron. Dosage will be based on Hb level and patient body weight.

Intervention Type: DRUG

Folic acid

Anemic patients with folate deficiency will receive folic acid 5 mg per day for 1 month

Intervention Type: DRUG

B12

Anemic patients with B12 deficiency will receive B vitamin complex 1 tablet per day for 1 month

Intervention Type: DRUG

Other Intervention Names

i.v. iron; Folate; cobalamin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda Ospedaliera Universitaria Integrata Verona

OTHER

Sponsor Role: lead

Responsible Party

Fabiana Busti

Clinical researcher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Azienda Ospedaliera Universitaria Integrata di Verona

Verona, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Domenico Girelli, MD

Role: CONTACT

domenico.girelli@univr.it

+39 0458125262

Fabiana Busti, MD

Role: CONTACT

fabiana.busti@univr.it

+ 39 0458126030

Facility Contacts

Domenico Girelli, Prof.

Role: primary

domenico.girelli@aovr.veneto.it

+ 39 0458124262

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Calleja JL, Delgado S, del Val A, Hervas A, Larraona JL, Teran A, Cucala M, Mearin F; Colon Cancer Study Group. Ferric carboxymaltose reduces transfusions and hospital stay in patients with colon cancer and anemia. Int J Colorectal Dis. 2016 Mar;31(3):543-51. doi: 10.1007/s00384-015-2461-x. Epub 2015 Dec 22.

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Other Identifiers

CO-2016-02361206

Identifier Type: -

Identifier Source: org_study_id