Beta thalassemia is a significant global health burden, particularly in regions with high prevalence due to genetic factors. Transfusion dependency remains the cornerstone of managing severe beta thalassemia, but it is associated with complications such as iron overload and alloimmunization, necessitating alternative therapeutic approaches. Hydroxyurea and thalidomide have shown potential in increasing fetal hemoglobin levels and reducing transfusion requirements in these patients. However, the relative efficacy and safety of these agents as monotherapies or in combination have not been adequately compared. This study aims to address this gap by evaluating these therapeutic strategies in a rigorously designed randomized controlled trial.

Objectives

• To compare the efficacy of single agent thalidomide, and the combination of thalidomide and hydroxyurea in reducing transfusion requirements among children with transfusion-dependent beta thalassemia.

• To compare the safety profiles of these therapeutic regimens.

• To evaluate the impact of these treatments on quality of life and hematological parameters, including hemoglobin levels and fetal hemoglobin production.

Methodology

• Study Design: Prospective, randomized, open-label, parallel controlled trial.

• Study Population:

o Inclusion Criteria: Children more than 5 years with transfusion-dependent beta-thalassemia.

o Exclusion Criteria: Pregnancy, significant comorbidities, or hypersensitivity to study drugs.

• Interventions:

o Group A: Thalidomide monotherapy (standard dosing based on clinical guidelines).

o Group B: Combination of hydroxyurea and thalidomide (optimized doses for combination therapy).

• Randomization and Blinding: Patients will be randomized in a 1:1 ratio. The trial will be open-label due to the differing regimens but will include blinded outcome assessors.

• Duration: 12 months of treatment with a follow-up period of 6 months.

• Outcome Measures:

o Primary Outcome: Reduction in transfusion requirements (measured as units of blood transfused over 12 months).

o Secondary Outcomes: Hemoglobin levels, fetal hemoglobin percentage, adverse events, and quality of life (measured using a validated questionnaire).

• Data Analysis:  Statistical comparisons will be made using ANOVA for continuous variables and chi-square tests for categorical variables.

4. Expected Outcomes

• Identification of the most effective regimen in reducing transfusion dependency among adult beta thalassemia patients.

• Comprehensive safety profile of hydroxyurea, thalidomide, and their combination.

• Insights into the potential synergistic effects of combined therapy on fetal hemoglobin production.

• Enhanced understanding of how these treatments impact quality of life of thalassemia patients.

The findings from this study could provide critical evidence to guide therapeutic decision-making and improve outcomes for transfusion-dependent beta thalassemia patients globally.