Ferric Carboxymaltose With or Without Phosphate Substitution for the Treatment of Iron Deficiency or Iron Deficiency Anemia

Ferric Carboxymaltose With or Without Phosphate Substitution for the Treatment of Iron Deficiency or Iron Deficiency Anemia Before Elective Surgery - the DeFICIT Trial

This is a confirmatory trial to establish superior serum phosphate stability associated with use of Phoscap® compared with placebo as a supplement for treatment of iron deficiency or iron deficiency anemia with Ferinject® before elective surgery.

Study Overview

• Status: Completed
• Conditions: Iron-deficiency; Anemia; Hypophosphatemia
• Intervention / Treatment: Drug: Verum; Drug: Placebo

Detailed Description

Iron deficiency anemia is a global health problem most commonly caused by excessive blood loss, impaired intestinal iron absorption, or chronic inflammation. In the perioperative setting, intravenous ferric carboxymaltose allows efficient treatment of preoperative iron deficiency and anemia. Recent studies have implied that ferric carboxymaltose might cause hypophosphatemia. Notably, hypophosphatemia has been associated with less muscle strength, which may influence early post-surgery recovery of patients. Additional oral phosphate supplementation may alleviate this hypophosphatemia.

This is a confirmatory trial to establish superior serum phosphate stability associated with use of Phoscap® compared with placebo as a supplement for treatment of iron deficiency or iron deficiency anemia with Ferinject® before elective surgery.

This is also a confirmatory trial to establish non-inferior efficacy of Phoscap® compared with placebo for the treatment of iron deficiency or iron deficiency anemia with Ferinject®; and to establish superior core muscle strength associated with the use of Phoscap® compared with placebo.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Alexander Kaserer, PD Dr.; Phone Number: +41442551111; Email: alexander.kaserer@usz.ch
• Study Contact Backup: Name: Donat R Spahn, Prof. Dr.; Phone Number: +41432532695; Email: donat.spahn@usz.ch

Study Locations

• Switzerland
  • Zurich, Switzerland, 8091
    • University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Informed Consent as documented by signature (Appendix 5: Informed Consent Form)
• Male or female ASA 1 to 3 patients, at least 18 years old
• Scheduled for an elective major abdominal or thoracic surgery.
• Patients with isolated iron deficiency (defined as hemoglobin concentration (Hb) > 130 g/l, and plasma Ferritin < 100 ng/ml or TSAT < 20%), or iron deficiency anemia (defined as Hb 100-130 g/l, and plasma Ferritin < 100 ng/ml or TSAT < 20%).
• Patients scheduled to be hospitalized ≥ 3 days.

Exclusion Criteria:

• Patients with known anaphylactic reactions to parenteral iron products. Patients with allergy/hypersensitivity to any contents of Ferinject® or Phoscap®.
• Patients with iron overload or disturbances in utilization of iron (e.g. haemochromatosis, hemosiderosis).
• Patients with ≥3 times increase in aspartate aminotransferase or alanine aminotransferase as per reference range.
• Patients with excessive blood loss requiring massive transfusion (≥ 10 more red blood cell units).
• Patients with known myelodysplastic syndromes.
• Patients with chronic kidney disease with an estimated GFR < 30 ml/min or with end-stage renal disease requiring scheduled dialysis.
• Patients with known urinary tract infections with urea-splitting bacteria.
• Patients with known diseases influencing phosphate, calcium or vitamin D homeostasis (e.g. Hyperparathyroidism, X-linked hypophosphatemia, renal tubular acidosis).
• Patients taking medication significantly influencing phosphate, calcium or vitamin D homeostasis (e.g. vitamin D substitution > 800 I.E. per day in the last 4 months, pre-existing phosphate substitution, phosphate binders).
• Patients with preexisting hypophosphatemia
• Any patient judged to lack the ability to give informed consent or perform the trial assessments (e.g. due to dementia, insufficient knowledge of the German language).
• Women who are pregnant or breast feeding,
• Intention to become pregnant during the course of the study,
• Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases (Female participants who are surgically sterilized / hysterectomized or post-menopausal for longer than 2 years are not considered as being of child bearing potential),
• Known or suspected non-compliance, drug or alcohol abuse.
• Participation in another study with investigational drug within the 30 days preceding and during the present study.
• Any patient judged by the Principal Investigator or Sub-Investigator to be inappropriate for the trial for any other reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; The participant takes wo capsules Placebo orally three times a day over 30 days beginning the day of Ferinject administration.
Experimental: Verum	Drug: Verum; The participant takes two capsules Phoscap® (3mmol/capsule) orally three times a day over 30 days beginning the day of Ferinject administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish superior serum phosphate stability	The primary endpoint is superior serum phosphate stability. The investigators measure perioperative phosphate concentrations in participants during the follow-up visits and compare the results between verum and placebo group.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative hemoglobin concentration	Mean perioperative Hb of the day of surgery, post-operative day (POD)2 and POD4.	3 years
Core muscle strength	Pre- and postoperative assessment of core muscle strength by volitional testing of maximal inspiratory and expiratory pressures.	3 years

Collaborators and Investigators

• Sponsor: Donat R. Spahn
• Collaborators: University of Zurich
• Investigators: Principal Investigator: Donat R Spahn, Prof. Dr., University of Zurich

Publications and helpful links

General Publications

• Munoz M, Laso-Morales MJ, Gomez-Ramirez S, Cadellas M, Nunez-Matas MJ, Garcia-Erce JA. Pre-operative haemoglobin levels and iron status in a large multicentre cohort of patients undergoing major elective surgery. Anaesthesia. 2017 Jul;72(7):826-834. doi: 10.1111/anae.13840. Epub 2017 Apr 6.
• Wolf M, Koch TA, Bregman DB. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res. 2013 Aug;28(8):1793-803. doi: 10.1002/jbmr.1923.
• Munoz M, Gomez-Ramirez S, Campos A, Ruiz J, Liumbruno GM. Pre-operative anaemia: prevalence, consequences and approaches to management. Blood Transfus. 2015 Jul;13(3):370-9. doi: 10.2450/2015.0014-15. Epub 2015 Jun 16. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Actual): May 9, 2023
• Study Completion (Actual): May 23, 2023

Study Registration Dates

• First Submitted: October 14, 2021
• First Submitted That Met QC Criteria: October 27, 2021
• First Posted (Actual): October 28, 2021

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: elective surgery; iron-deficiency anemia; hypophosphatemia; iron-deficiency; preoperative iron substitution; phosphate substitution
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Phosphorus Metabolism Disorders; Anemia, Iron-Deficiency; Anemia; Hypophosphatemia; Iron Deficiencies
• Other Study ID Numbers: 2021-00383

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