Do Iron And Vitamin B12 Injections Given Together, Improve Hemoglobin In Patients On Hemodialysis?

Study Overview
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Brief Summary
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A parallel group, quadruple blind, placebo-controlled, randomized control trial with 2x2 factorial design to determine the effect of simultaneous IV ferric carboxymaltose and IM hydroxycobalamin supplementation in anemic Indian HD patients

Official Title
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The Role Of IV Iron (Ferric Carboxymaltose) And IM Vitamin B12 (Hydroxycobalamin) Supplementation In The Management Of Anaemic Prevalent Indian Hemodialysis Patients: A Parallel Group, Quadruple Blind, Placebo-Controlled, Pragmatic Randomized Control Trial With 2x2 Factorial Design

Conditions
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Iron Deficiency Anemia, B12 Deficiency Anemia

Intervention / Treatment
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* Drug: Ferric carboxymaltose
* Drug: Hydroxycobalamin
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All adult prevalent HD patients on HD for at least 3 months with hemoglobin < 11 g/dL Exclusion Criteria: Blood transfusion, blood loss, infection, surgery or change in haemoglobin by > 1 g/dL in the last 1 month Hemoglobinopathy Cirrhosis Hematological malignancy or myeloproliferative disorder HIV, HBV or HCV infection Any chronic inflammatory disorder IV iron or oral/IM B12 received in the last 3 months Severe hyperparathyroidism (intact parathyroid hormone > 1,000 pg/mL) Pregnancy Age < 18 years History of asthma or eczema, any history of drug allergy, including allergy to iron preparations History of exposure to chemotherapy or cytotoxic drugs - 5-FU, hydroxyurea, hydroxycarbamide, methotrexate, trimethoprim, colchicine, azathioprine History of G-CSF use in the last 1 month General anaesthesia with nitrous oxide in the last 1 month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Factorial Assignment
Interventional Model Description: Participants will be randomized to one of four arms: IV ferric carboxymaltose + placebo, IM hydroxycobalamin + placebo, IV ferric carboxymaltose + IM hydroxycobalamin, placebo + placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FCM + placebo<br>Ferric carboxymaltose: Single dose, 500 mg Placebo: Single dose | Drug: Ferric carboxymaltose<br>* Single dose of ferric carboxymaltose (Encicarb, Emcure Pharmaceuticals Ltd., Pune, India) 500 mg administered intravenously in 100 ml normal saline over 1 hour via the dialysis blood line immediately following HD<br>Drug: Placebo<br>* Single dose of 1 ml of distilled water injected intramuscularly in the deltoid of the non-fistula arm immediately following HD<br>|
| Experimental: B12 + placebo<br>Hydroxycobalamine: Single dose, 1000 mcg Placebo: Single dose | Drug: Hydroxycobalamin<br>* Single dose of hydroxycobalamine (Trineurosol Hp, Tridoss Laboratories, Mumbai, India) 1000 mcg administered intramuscularly in the deltoid of the non-fistula arm immediately following HD<br>Drug: Placebo<br>* Single dose of 100 ml normal saline administered intravenously over 1 hour via the dialysis blood line immediately following HD<br>|
| Experimental: FCM +B12<br>Ferric carboxymaltose: Single dose, 500 mg Hydroxycobalamine: Single dose, 1000 mcg | Drug: Ferric carboxymaltose<br>* Single dose of ferric carboxymaltose (Encicarb, Emcure Pharmaceuticals Ltd., Pune, India) 500 mg administered intravenously in 100 ml normal saline over 1 hour via the dialysis blood line immediately following HD<br>Drug: Hydroxycobalamin<br>* Single dose of hydroxycobalamine (Trineurosol Hp, Tridoss Laboratories, Mumbai, India) 1000 mcg administered intramuscularly in the deltoid of the non-fistula arm immediately following HD<br>|
| Placebo Comparator: Placebo + placebo<br>Placebo: Single dose Placebo: Single dose | Drug: Placebo<br>* Single dose of 1 ml of distilled water injected intramuscularly in the deltoid of the non-fistula arm immediately following HD<br>Drug: Placebo<br>* Single dose of 100 ml normal saline administered intravenously over 1 hour via the dialysis blood line immediately following HD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean haemoglobin | Mean haemoglobin measured 30 days after the intervention | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity and specificity of baseline automated red cell indices, peripheral smear red cell indices, and iron indices for diagnosis of iron deficiency | Sensitivity and specificity of baseline peripheral smear hypochromic RBCs >10%, peripheral smear red blood cell anisocytosis > 10%, percentage hypochromic mature red cells (%HYPOm) >6%, reticulocyte hemoglobin content (CHr) < 30 pg, transferrin saturation (TSAT), and serum ferritin, for the diagnosis of iron deficiency anemia. Iron deficiency anemia is defined by an increase in corrected reticulocyte index (reticulocyte % x hematocrit/40) >1% at 7 days and/or increase in hemoglobin by ≥1 g/dL 30 days after administration of IV FCM in the FCM +placebo arm. | Baseline | 
| Optimum cutoff for baseline automated red cell indices for the diagnosis of iron deficiency anemia using ROC curve analysis | Optimum cutoff of baseline %HYPOm and CHr for the diagnosis of iron deficiency anemia using ROC curve analysis. Iron deficiency anemia is defined by an increase in corrected reticulocyte index (reticulocyte % x hematocrit/40) >1% at 7 days and/or increase in hemoglobin by ≥1 g/dL 30 days after administration of IV FCM in the FCM +placebo arm. | Baseline | 
| Sensitivity and specificity of baseline peripheral blood smear hypochromia, peripheral blood smear anisocytosis and automated red cell indices for the diagnosis of iron deficiency anemia in participants with TSAT < 30% and TSAT > =30%. | Sensitivity and specificity of > 10% hypochromic red blood cells on peripheral blood smear, >10% red blood cell anisocytosis on peripheral blood smear, %HYPOm > 6%, and CHr < 30 pg measured at baseline, for the diagnosis of iron deficiency anemia in participants with baseline TSAT < 30% and TSAT > 30% respectively. Iron deficiency anemia is defined by an increase in corrected reticulocyte index (reticulocyte % x hematocrit/40) >1% at 7 days and/or increase in hemoglobin by ≥1 g/dL 30 days after administration of IV FCM in the FCM +placebo arm. | Baseline | 
| Sensitivity and specificity of baseline peripheral smear neutrophil hypersegmentation and cell population data for the diagnosis of B12 deficiency. | Sensitivity and specificity of baseline peripheral smear neutrophil hypersegmentation (>3 percent of neutrophils with ≥5 lobes or ≥1 neutrophil with ≥6 lobes per 100 neutrophils) and cell population data [mean neutrophil volume > 145 fl or mean monocyte volume > 168 fl] for the diagnosis of B12 deficiency. B12 deficiency is defined as an increase in corrected reticulocyte index > 1% (reticulocyte % x hematocrit/40) at 7 days and/or increase in hemoglobin by ≥1 g/dL 30 days after administration of IM hydroxycobalamin in the B12 + placebo group. | Baseline | 
| Optimum cutoff of cell population data for the diagnosis of B12 deficiency using ROC curve analysis | Optimum cutoff of baseline mean neutrophil volume and mean monocyte volume for the diagnosis of B12 deficiency using ROC curve analysis. B12 deficiency is defined as an increase in corrected reticulocyte index > 1% (reticulocyte % x hematocrit/40) at 7 days and/or increase in hemoglobin by ≥1 g/dL 30 days after administration of IM hydroxycobalamin in the B12 + placebo group. | Baseline | 
| Adverse effects of IV ferric carboxymaltose and IM hydroxycobalamin therapy | Any adverse events attributable to the use of IV ferric carboxymaltoise and/or IM hydroxycobalamin | Day 0 |