Hydoxycarbamide and L-Carnitine Therapy in Sickle Cell Anemia

Treatment With Hydoxycarbamide and L-Carnitine in Adult Patients With Severe Forms of Sickle Cell Anemia: An Overview

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

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Hydroxycarbamide 500 Mg Oral Capsule+L-Carnitine; Drug: Hydroxycarbamide 500 Mg Oral Capsule; Drug: L-Carnitine, 250 Mg Oral Capsule

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt, 71515
    • Safaa A A Khaled

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydra+L-Carnitine; Hydroxycarbamide+ L-Carnitine+supportive treatment	Drug: Hydroxycarbamide 500 Mg Oral Capsule+L-Carnitine; Combination therapy; Other Names: Hydroxyurea+LC
Active Comparator: Hydra only; Hydroxycarbamide+ supportive treatment	Drug: Hydroxycarbamide 500 Mg Oral Capsule; Single agent; Other Names: Hydroxyurea
Active Comparator: L-Carnitine only; L-Carnitine+ supportive treatment	Drug: L-Carnitine, 250 Mg Oral Capsule; single agent; Other Names: L-Carnitine
No Intervention: Supportive measures; Supportive only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematological(HR)	Change of hemoglobin	2-3 months
Hematological response	Change of hematocrit	2-3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of painful episodes/ blood transfusions	Change of frequency of painful episodes and blood transfusion	1-year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delayed effects	effect on long term complications as cardiovascular and cerebrovascular ones	12-18 months

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Director: Israa EM Ashry, Prof, Assiut University- Faculty of Medicine

Publications and helpful links

General Publications

• Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994 Jun 9;330(23):1639-44. doi: 10.1056/NEJM199406093302303.
• Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010 Dec 11;376(9757):2018-31. doi: 10.1016/S0140-6736(10)61029-X. Epub 2010 Dec 3.
• Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997 Sep 11;337(11):762-9. doi: 10.1056/NEJM199709113371107. No abstract available.
• Kauf TL, Coates TD, Huazhi L, Mody-Patel N, Hartzema AG. The cost of health care for children and adults with sickle cell disease. Am J Hematol. 2009 Jun;84(6):323-7. doi: 10.1002/ajh.21408.
• Elmariah H, Garrett ME, De Castro LM, Jonassaint JC, Ataga KI, Eckman JR, Ashley-Koch AE, Telen MJ. Factors associated with survival in a contemporary adult sickle cell disease cohort. Am J Hematol. 2014 May;89(5):530-5. doi: 10.1002/ajh.23683. Epub 2014 Feb 21.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2017
• Primary Completion (Actual): June 10, 2020
• Study Completion (Actual): July 10, 2021

Study Registration Dates

• First Submitted: September 24, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Actual): October 22, 2021
• Last Update Submitted That Met QC Criteria: October 15, 2021
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antisickling Agents; Hydroxyurea
• Other Study ID Numbers: SKhaled2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes