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

Primary Purpose

Iron Deficiency Anemia, B12 Deficiency Anemia

Status
Unknown status
Phase
Phase 4
Locations
India
Study Type
Interventional
Intervention
Ferric carboxymaltose
Hydroxycobalamin
Placebo
Placebo
Sponsored by
Christian Medical College, Vellore, India
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Iron Deficiency Anemia

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Christian Medical College, VelloreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

FCM + placebo

B12 + placebo

FCM +B12

Placebo + placebo

Arm Description

Ferric carboxymaltose: Single dose, 500 mg Placebo: Single dose

Hydroxycobalamine: Single dose, 1000 mcg Placebo: Single dose

Ferric carboxymaltose: Single dose, 500 mg Hydroxycobalamine: Single dose, 1000 mcg

Placebo: Single dose Placebo: Single dose

Outcomes

Primary Outcome Measures

Mean haemoglobin
Mean haemoglobin measured 30 days after the intervention

Secondary Outcome Measures

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.
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.
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.
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.
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.
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

Full Information

First Posted
November 8, 2020
Last Updated
January 28, 2021
Sponsor
Christian Medical College, Vellore, India
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1. Study Identification

Unique Protocol Identification Number
NCT04627181
Brief Title
Do Iron And Vitamin B12 Injections Given Together, Improve Hemoglobin In Patients On Hemodialysis?
Acronym
ALOHA
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 18, 2020 (Actual)
Primary Completion Date
March 2021 (Anticipated)
Study Completion Date
March 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Christian Medical College, Vellore, India

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Iron Deficiency Anemia, B12 Deficiency Anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Factorial Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
FCM + placebo
Arm Type
Experimental
Arm Description
Ferric carboxymaltose: Single dose, 500 mg Placebo: Single dose
Arm Title
B12 + placebo
Arm Type
Experimental
Arm Description
Hydroxycobalamine: Single dose, 1000 mcg Placebo: Single dose
Arm Title
FCM +B12
Arm Type
Experimental
Arm Description
Ferric carboxymaltose: Single dose, 500 mg Hydroxycobalamine: Single dose, 1000 mcg
Arm Title
Placebo + placebo
Arm Type
Placebo Comparator
Arm Description
Placebo: Single dose Placebo: Single dose
Intervention Type
Drug
Intervention Name(s)
Ferric carboxymaltose
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Hydroxycobalamin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Single dose of 1 ml of distilled water injected intramuscularly in the deltoid of the non-fistula arm immediately following HD
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Single dose of 100 ml normal saline administered intravenously over 1 hour via the dialysis blood line immediately following HD
Primary Outcome Measure Information:
Title
Mean haemoglobin
Description
Mean haemoglobin measured 30 days after the intervention
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Sensitivity and specificity of baseline automated red cell indices, peripheral smear red cell indices, and iron indices for diagnosis of iron deficiency
Description
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.
Time Frame
Baseline
Title
Optimum cutoff for baseline automated red cell indices for the diagnosis of iron deficiency anemia using ROC curve analysis
Description
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.
Time Frame
Baseline
Title
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%.
Description
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.
Time Frame
Baseline
Title
Sensitivity and specificity of baseline peripheral smear neutrophil hypersegmentation and cell population data for the diagnosis of B12 deficiency.
Description
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.
Time Frame
Baseline
Title
Optimum cutoff of cell population data for the diagnosis of B12 deficiency using ROC curve analysis
Description
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.
Time Frame
Baseline
Title
Adverse effects of IV ferric carboxymaltose and IM hydroxycobalamin therapy
Description
Any adverse events attributable to the use of IV ferric carboxymaltoise and/or IM hydroxycobalamin
Time Frame
Day 0
Other Pre-specified Outcome Measures:
Title
Exploratory: Sensitivity and specificity of red cell anisochromia on peripheral smear for the diagnosis of iron deficiency anemia
Description
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.
Time Frame
Baseline
Title
Optimal cutoff of baseline serum methylmalonic acid for the diagnosis of B12 deficiency
Description
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.
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna T Valson, MD, DM
Phone
+91-416-2282683
Email
annavalson@cmcvellore.ac.in
First Name & Middle Initial & Last Name or Official Title & Degree
Rizwan Alam, MD
Phone
+91-416-2282053
Email
rizwangb0557@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anna T Valson, MD, DM
Organizational Affiliation
Christian Medical College, Vellore, India
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Rizwan Alam, MD
Organizational Affiliation
Christian Medical College, Vellore, India
Official's Role
Principal Investigator
Facility Information:
Facility Name
Christian Medical College, Vellore
City
Vellore
State/Province
Tamil Nadu
ZIP/Postal Code
632004
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna T Valson, MD, DM
Phone
+919894143677
Email
annavalson@cmcvellore.ac.in
First Name & Middle Initial & Last Name & Degree
Rizwan Alam, MD
Phone
+918130560297
Email
rizwangb0557@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All individual participant data (including data dictionaries) will be made available immediately after publication of the trial results for an indefinite time period.
IPD Sharing Time Frame
Immediately after publication of the results, for an indefinite period
IPD Sharing Access Criteria
IPD will be made available to investigators whose proposed use of the data has been approved by an independent review committee in order to achieve aims in the approved proposal. Proposals should be directed to annavalson@cmcvellore.ac.in. To gain access, data requestors will need to sign a data access agreement. Data will be made available at the third party website.

Learn more about this trial

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

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