An Algorithm to Start Iron Chelation in Minimally Transfused Young Beta-thalassemia Major Patients

NCT02173951 | Unknown Phase 2 DMC

• 1 other identifier: start of ICT in young BTM
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective randomized study on Safety, Tolerability and Efficacy of oral Low dose DFP (50 mg/kg/day) in minimally transfused B-TM after 5 transfusions when SF reaches 500 ng/m and with either appearance of LPI \> 0.2 or TSAT reaches 50% compared with non treatment arm. So the aim of this study:

1. 1.To determine the time as well as amount of transfused iron ( calculated in mg iron/kg ) which lead to Serum ferritin reaches 500 ng /ml and LPI appearance \>0.2 as well as TSAT reaches 50 % .
2. 2.Tolerability and safety of early low dose DFP 50mg/kg and effectiveness to postpone or prevent SF from reaching 1000 ng/ml or LPI \>0.6 or TSAT \>70% in comparison to patients not starting chelation therapy
3. 3.Determine adverse events whether drug or non drug related

Conditions

Beta Thalassemia Major

Keywords

young minimally transfused beta thalassemia major; labile plasma iron (LPI); Transferrin saturation (TSAT); Deferiprone; Transfusional iron loading rate; Transfusion units

Outcome Measures

Primary Outcomes (1)

• determine the time and number of transfusion units as well as amount of infused iron that will lead to appearance of LPI >0.2 or TSAT>50 % , serum ferritin ≥ 500 ng/ml in the studied thalassemic patients which warrant start of iron chelation

  To determine the time as well as amount of transfused iron ( calculated in mg iron/kg ) at which there is LPI appearance of \>0.2 as well as TSAT reaching 70 %, a serum ferritin ≥ 500 in order to start Iron chelation therapy

  12 months

Secondary Outcomes (1)

• Evaluation of safety of early use of iron chelation Therapy (ICT) in terms of drug related AEs or SAEs

  12 months

Study Arms (2)

arm 1 iron chelation

ACTIVE COMPARATOR

Active Comparator arm : iron chelation Included 32 thalassemia major patients with low serum ferritin (≥500) . They will receive low dose Deferiprone( DFP )on 50 mg/kg/d.

Drug: Deferiprone

arm 2 blood transfusion

PLACEBO COMPARATOR

Placebo Comparator arm: blood transfusion only Included 32 thalassemia patients with low serum ferritin (≥500). They receive blood transfusion with no chelation. Patients will start deferiprone 75 mg/kg/d when reaching Primary end point which is elevation of SF to around 1000 ng/ml or more or Tsat \> 90 % and or LPI \> 0.6

Drug: Deferiprone

Interventions

Deferiprone DRUG

in arm 1 ( active comparator) will receive a starting dose of Deferiprone (DFP) 50mg⁄ kg ⁄ d, administered orally 3 times daily. Routine dose adjustments will be made according to serum ferritin trends and safety. Patients reaching serum ferritin ≥1000 will be subjected to dose escalation of DFP to 75 mg/kg/d. Patients in Placebo Comparator arm when reaching end point elevation of SF to around 1000 ng/ml or more or Tsat \> 90 % and or LPI \> 0.6 will start deferiprone 75 mg/kg/d

Also known as: ferriprox

arm 1 iron chelation; arm 2 blood transfusion

Eligibility Criteria

• Age: 6 Months - 36 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Young beta thalassemia major patients (diagnosed by HPLC, CBC) who started transfusion therapy who received 5-7transfusions or less, aged more than 6 months.
• Pre-transfusional Hb should be \>9 g/dL.
• Serum ferritin should be ≤ 500ng/ml, transferrin saturation ≤ 50%.

You may not qualify if:

• \. Beta thalassemia intermedia patients, patients with other transfusion dependent anemias (myelodysplasia, other chronic hemolytic anemias , pure red cell aplasia , aplastic anemia ) 2. Patients with levels of ALT \>5 the upper limit of normal (ULN), serum creatinine \> ULN on 2 measurements.
• \. Patients with history of agranulocytosis \[absolute neutrophil count (ANC) \<0.5×109/L\].
• \. Non complaint patients acknowledged by reviewing the patient's records.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Pediatric Hematology clinic, Ain Shams University

Cairo, Egypt

Location

Related Publications (2)

• Padhani ZA, Gangwani MK, Sadaf A, Hasan B, Colan S, Alvi N, Das JK. Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. Cochrane Database Syst Rev. 2023 Nov 17;11(11):CD011626. doi: 10.1002/14651858.CD011626.pub3.

  PMID: 37975597 DERIVED

• Elalfy MS, Adly A, Awad H, Tarif Salam M, Berdoukas V, Tricta F. Safety and efficacy of early start of iron chelation therapy with deferiprone in young children newly diagnosed with transfusion-dependent thalassemia: A randomized controlled trial. Am J Hematol. 2018 Feb;93(2):262-268. doi: 10.1002/ajh.24966. Epub 2017 Nov 27.

  PMID: 29119631 DERIVED

MeSH Terms

Conditions

beta-Thalassemia

Interventions

Deferiprone

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mohsen S Elalfy, professour

  Ain Shams University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amira AM Adly, Asst. prof

CONTACT

0105245837; amiradiabetes@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of pediatric

Study Record Dates

• First Submitted: June 23, 2014
• First Posted: June 25, 2014
• Study Start: July 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: January 14, 2015

Record last verified: 2015-01

Locations

EG (1)