"Hydroxyurea for the Treatment of Sickle Cell Anemia".

The New England Journal of Medicine. 1995. 332(20):1317-1322.
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Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
8.3 Further Monitoring
9 Funding
10 Further Reading

Clinical Question

In adults with sickle cell anemia, does hydroxyurea reduce the frequency of painful crises?

Bottom Line

In adults with sickle cell anemia and a history of three or more painful crises per year, treatment with hydroxyurea led to a 44% reduction in the median annual rate of painful crises and was associated with fewer incidents of chest syndrome and transfusions, without significant adverse effects.

Major Points

Hydroxyurea was shown to be the first clinically acceptable drug that could potentially prevent painful crises in adults with sickle cell anemia, marking a significant advancement in the management of this condition.

Guidelines

Current guidelines recommend considering hydroxyurea therapy for certain patients with sickle cell anemia to reduce the incidence of pain crises and acute chest syndrome, as well as mitigate the need for blood transfusions.

Design

- Double-blind, randomized, placebo-controlled clinical trial.
- N=299 adults with sickle cell anemia and history of three or more painful crises per year.

Population

Inclusion Criteria:
- Adults aged 18 or older
- Diagnosed with sickle cell anemia
- Reported at least three pain crises in the year prior to the study

Exclusion Criteria:
- Pregnancy
- Narcotic addiction or high regular consumption of narcotics
- Participation in long-term transfusion program
- Prior hydroxyurea therapy
- Presence of HIV antibodies
- Certain baseline blood count ranges indicating marrow depression

Baseline Characteristics:
- No significant differences between groups with respect to sex, age, race/ethnic group, number of α-globin genes, or β-globin haplotype.
- Similar blood counts before treatment initiation.

Interventions

- Hydroxyurea: Initial dose of 15 mg/kg/day, increased every 12 weeks up to 35 mg/kg/day unless myelotoxicity was present.
- Placebo group received an adjusted dose to maintain blinding.
- All patients received 1 mg folic acid per day.

Outcomes

Primary Outcome:
- Reduction in the frequency of painful crises.

Secondary Outcomes:
- Incidents of chest syndrome and transfusions.
- Safety and potential adverse effects, including myelotoxicity.

Further Monitoring
- Hemoglobin levels, mean corpuscular volumes, fetal hemoglobin levels, and proportions of F cells at follow-up.
- Monitoring for long-term safety, including risks of leukemogenesis.

Funding

Supported by cooperative agreements with the National Heart, Lung, and Blood Institute and General Clinical Research Center grants; assistance from Bristol-Myers Squibb.

Further Reading

- Details and participating institutions listed in the Appendix.