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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Anemia, Iron-deficiency, Hypophosphatemia

Intervention / Treatment
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* Drug: Verum
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iron-deficiency anemia, hypophosphatemia, elective surgery, iron-deficiency, preoperative iron substitution, phosphate substitution