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Hydoxycarbamide and L-Carnitine Therapy in Sickle Cell Anemia

A

Assiut University

Status and phase

Completed
Phase 4

Conditions

Sickle Cell Disease

Treatments

Drug: L-Carnitine, 250 Mg Oral Capsule
Drug: Hydroxycarbamide 500 Mg Oral Capsule+L-Carnitine
Drug: Hydroxycarbamide 500 Mg Oral Capsule

Study type

Interventional

Funder types

Other

Identifiers

NCT05081349
SKhaled2021

Details and patient eligibility

About

The role of the combination therapy of hydroxyurea and L-Carnitine was studied in thalassemic patients. nevertheless its role in sickle cell anemia patients was not investigated

Full description

Sickle cell disease (SCD) is a common monogenic disorder affecting over 100,000 people in the United States alone, and millions more worldwide. This often devastating disease is characterized by red blood cell (RBC) sickling; chronic hemolytic anemia; episodic vaso-occlusion associated with severe pain and inflammation; acute and cumulative organ damage that manifests as stroke, acute chest syndrome, sickle lung disease, pulmonary hypertension nephropathy and end-stage renal disease; and other chronic morbidities.

Lives of patients with SCD are characterized by frequent episodes of severe pain (vaso-occlusive events or "crises"); acute organ dysfunction, including a pneumonia-like syndrome termed acute chest syndrome, and strokes starting in childhood; and progressive multi-organ damage. Not surprisingly, patients with SCD have very high health care utilization (over $1 billion/year in healthcare costs in the United States alone, and a median life-expectancy of only ~45-58 years, compared to the life expectancy of 78.2 years overall in the United States.

Although it is licensed in the United States for administration to sickle cell patients who have ≥ 3 crises a year in steady state, hydroxyurea (HU) remains unlicensed in most countries where it is regarded as an experimental drug In those areas, where HU is unlicensed for SCD, it is offered to patients who have ≥ 5 crises a year; or 3-4 crises a year with either neutrophil count ≥ 10 × 109/L or platelet count ≥ 500 × 109/L in steady state ; bearing in mind that the reference range for neutrophil count in black people is 1-3 × 109/L, and is 100-300 × 109/L for platelets .

Since high neutrophil count in steady state is a marker of severe SCD , these criteria usually identify individuals who have a clinical course sufficiently severe to ensure that the benefits of hydroxyurea therapy justify the potential risks. HU therapy is offered if the patient does not want to have (more) children, and is weighed against any severe impairment of liver or kidney function, or blood cytopenia. HU is unlicensed in most countries because the long-term adverse effects are unknown, not because the clinical efficacy is in doubt. In fact, after over 9 years of follow-up, HbSS subjects who received HU in the US placebo-controlled trial, had significantly less painful crises, acute chest syndrome, and mortality . Potential long-term toxic effects that reduce enthusiasm for HU include teratogenicity, carcinogenesis and, for young children, impaired cognitive development.

Enrollment

91 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Patients with sickle cell disease
  • Not welling for pregnancy in females or to father a baby in males
  • Frequent episodes
  • Non-compliance to transfusion

Exclusion criteria

  • <18 years
  • Hypersensitivity to hydroxycarbamide or L-Carnitine
  • Pregnancy
  • Other chronic infection or inflammation

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

91 participants in 4 patient groups

Hydra+L-Carnitine
Experimental group
Description:
Hydroxycarbamide+ L-Carnitine+supportive treatment
Treatment:
Drug: Hydroxycarbamide 500 Mg Oral Capsule+L-Carnitine
Hydra only
Active Comparator group
Description:
Hydroxycarbamide+ supportive treatment
Treatment:
Drug: Hydroxycarbamide 500 Mg Oral Capsule
L-Carnitine only
Active Comparator group
Description:
L-Carnitine+ supportive treatment
Treatment:
Drug: L-Carnitine, 250 Mg Oral Capsule
Supportive measures
No Intervention group
Description:
Supportive only

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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