B12 Deficiency Anemia, Iron Deficiency Anemia
Conditions
Brief summary
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
Interventions
DRUGFerric carboxymaltose
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
DRUGHydroxycobalamin
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
DRUGPlacebo
Single dose of 1 ml of distilled water injected intramuscularly in the deltoid of the non-fistula arm immediately following HD
Sponsors
Christian Medical College, Vellore, India
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean haemoglobin | 30 days | Mean haemoglobin measured 30 days after the intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse effects of IV ferric carboxymaltose and IM hydroxycobalamin therapy | Day 0 | Any adverse events attributable to the use of IV ferric carboxymaltoise and/or IM hydroxycobalamin |
| Sensitivity and specificity of baseline peripheral smear neutrophil hypersegmentation and cell population data for the diagnosis of B12 deficiency. | Baseline | 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. |
| Optimum cutoff of cell population data for the diagnosis of B12 deficiency using ROC curve analysis | Baseline | 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. |
| Sensitivity and specificity of baseline automated red cell indices, peripheral smear red cell indices, and iron indices for diagnosis of iron deficiency | Baseline | 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. |
| Optimum cutoff for baseline automated red cell indices for the diagnosis of iron deficiency anemia using ROC curve analysis | Baseline | 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. |
| 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%. | Baseline | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Optimal cutoff of baseline serum methylmalonic acid for the diagnosis of B12 deficiency | Baseline | Optimal cutoff of baseline serum methylmalonic acid 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. 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. |
| Exploratory: Sensitivity and specificity of red cell anisochromia on peripheral smear for the diagnosis of iron deficiency anemia | Baseline | Sensitivity and specificity of red cell anisochromia \>=25% on the baseline peripheral smear 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. |
Countries
India
Contacts
Primary ContactAnna T Valson, MD, DM
Backup ContactRizwan Alam, MD
Outcome results
None listed