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1.
Bull World Health Organ ; 98(12): 859-868, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33293746

RESUMO

Objective: To determine the regional- and district-level newborn prevalence of sickle cell trait and disease, and the prevalence of haemoglobin variants and genetic modifiers of sickle cell disease, in the nine regions of north-western United Republic of Tanzania. Methods: We repurposed dried blood spot samples from children (aged 0-24 months) born to mothers living with human immunodeficiency virus (HIV), collected as part of the HIV Early Infant Diagnosis programme, for sickle cell diagnosis. We performed isoelectric focusing to determine whether samples had normal haemoglobin, sickle cell trait, sickle cell disease or a rare haemoglobin variant. We shipped samples diagnosed as disease or variant to Cincinnati Children's Hospital in the United States of America for deoxyribonucleic-acid-based analyses to determine the prevalence of α-thalassaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency or fetal haemoglobin genetic modifiers. Findings: We analysed a total of 17 200 specimens during February 2017-May 2018. We observed a prevalence of sickle cell trait and disease of 20.3% (3492/17 200) and 1.2% (210/17 200), respectively. District-level trait varied from 8.6% (5/58) to 28.1% (77/274). Among confirmed sickle cell disease specimens, we noted 42.7% (61/143) had 1-gene deletion and 14.7% (21/143) had 2-gene deletion α-thalassaemia trait. We documented G6PD A- deficiency in 19.2% (14/73) of males. Conclusion: Our calculated prevalence is twice as high as previously reported and reinforces the need for enhanced sickle cell diagnostic services. Our district-level data will inform public health policy, allowing screening and disease-modifying hydroxyurea therapy to be focused on high-prevalence areas, until universal newborn screening is available.

2.
Trials ; 21(1): 983, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33246482

RESUMO

BACKGROUND: Sickle cell disease (SCD) is a severe and devastating hematological disorder that affects over 100,000 persons in the USA and millions worldwide. Hydroxyurea is the primary disease-modifying therapy for the SCD, with proven benefits to reduce both short-term and long-term complications. Despite the well-described inter-patient variability in pharmacokinetics (PK), pharmacodynamics, and optimal dose, hydroxyurea is traditionally initiated at a weight-based dose with a subsequent conservative dose escalation strategy to avoid myelosuppression. Because the dose escalation process is time consuming and requires frequent laboratory checks, many providers default to a fixed dose, resulting in inadequate hydroxyurea exposure and suboptimal benefits for many patients. Results from a single-center trial of individualized, PK-guided dosing of hydroxyurea for children with SCD suggest that individualized dosing achieves the optimal dose more rapidly and provides superior clinical and laboratory benefits than traditional dosing strategies. However, it is not clear whether these results were due to individualized dosing, the young age that hydroxyurea treatment was initiated in the study, or both. The Hydroxyurea Optimization through Precision Study (HOPS) aims to validate the feasibility and benefits of this PK-guided dosing approach in a multi-center trial. METHODS: HOPS is a randomized, multicenter trial comparing standard vs. PK-guided dosing for children with SCD as they initiate hydroxyurea therapy. Participants (ages 6 months through 21 years), recruited from 11 pediatric sickle cell centers across the USA, are randomized to receive hydroxyurea either using a starting dose of 20 mg/kg/day (Standard Arm) or a PK-guided dose (Alternative Arm). PK data will be collected using a novel sparse microsampling approach requiring only 10 µL of blood collected at 3 time-points over 3 h. A protocol-guided strategy more aggressive protocols is then used to guide dose escalations and reductions in both arms following initiation of hydroxyurea. The primary endpoint is the mean %HbF after 6 months of hydroxyurea. DISCUSSION: HOPS will answer important questions about the clinical feasibility, benefits, and safety of PK-guided dosing of hydroxyurea for children with SCD with potential to change the treatment paradigm from a standard weight-based approach to one that safely and effectively optimize the laboratory and clinical response. TRIAL REGISTRATION: ClinicalTrials.gov NCT03789591 . Registered on 28 December 2018.

3.
N Engl J Med ; 382(26): 2524-2533, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32579813

RESUMO

BACKGROUND: Hydroxyurea has proven safety, feasibility, and efficacy in children with sickle cell anemia in sub-Saharan Africa, with studies showing a reduced incidence of vaso-occlusive events and reduced mortality. Dosing standards remain undetermined, however, and whether escalation to the maximum tolerated dose confers clinical benefits that outweigh treatment-related toxic effects is unknown. METHODS: In a randomized, double-blind trial, we compared hydroxyurea at a fixed dose (approximately 20 mg per kilogram of body weight per day) with dose escalation (approximately 30 mg per kilogram per day). The primary outcome was a hemoglobin level of 9.0 g or more per deciliter or a fetal hemoglobin level of 20% or more after 24 months. Secondary outcomes included the incidences of malaria, vaso-occlusive crises, and serious adverse events. RESULTS: Children received hydroxyurea at a fixed dose (94 children; mean [±SD] age, 4.6±1.0 years) or with dose escalation (93 children; mean age, 4.8±0.9 years); the mean doses were 19.2±1.8 mg per kilogram per day and 29.5±3.6 mg per kilogram per day, respectively. The data and safety monitoring board halted the trial when the numbers of clinical events were significantly lower among children receiving escalated dosing than among those receiving a fixed dose. At trial closure, 86% of the children in the dose-escalation group had reached the primary-outcome thresholds, as compared with 37% of the children in the fixed-dose group (P<0.001). Children in the dose-escalation group had fewer sickle cell-related adverse events (incidence rate ratio, 0.43; 95% confidence interval [CI], 0.34 to 0.54), vaso-occlusive pain crises (incidence rate ratio, 0.43; 95% CI, 0.34 to 0.56), cases of acute chest syndrome or pneumonia (incidence rate ratio, 0.27; 95% CI, 0.11 to 0.56), transfusions (incidence rate ratio, 0.30; 95% CI, 0.20 to 0.43), and hospitalizations (incidence rate ratio, 0.21; 95% CI, 0.13 to 0.34). Laboratory-confirmed dose-limiting toxic effects were similar in the two groups, and there were no cases of severe neutropenia or thrombocytopenia. CONCLUSIONS: Among children with sickle cell anemia in sub-Saharan Africa, hydroxyurea with dose escalation had superior clinical efficacy to that of fixed-dose hydroxyurea, with equivalent safety. (Funded by the Doris Duke Charitable Foundation and the Cincinnati Children's Research Foundation; NOHARM MTD ClinicalTrials.gov number, NCT03128515.).


Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/administração & dosagem , Hidroxiureia/administração & dosagem , Anemia Falciforme/complicações , Antidrepanocíticos/efeitos adversos , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Hidroxiureia/efeitos adversos , Incidência , Malária/epidemiologia , Masculino , Doenças Vasculares Periféricas/etiologia , Doenças Vasculares Periféricas/prevenção & controle , Estudos Prospectivos , Uganda
5.
N Engl J Med ; 380(2): 121-131, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30501550

RESUMO

BACKGROUND: Hydroxyurea is an effective treatment for sickle cell anemia, but few studies have been conducted in sub-Saharan Africa, where the burden is greatest. Coexisting conditions such as malnutrition and malaria may affect the feasibility, safety, and benefits of hydroxyurea in low-resource settings. METHODS: We enrolled children 1 to 10 years of age with sickle cell anemia in four sub-Saharan countries. Children received hydroxyurea at a dose of 15 to 20 mg per kilogram of body weight per day for 6 months, followed by dose escalation. The end points assessed feasibility (enrollment, retention, and adherence), safety (dose levels, toxic effects, and malaria), and benefits (laboratory variables, sickle cell-related events, transfusions, and survival). RESULTS: A total of 635 children were fully enrolled; 606 children completed screening and began receiving hydroxyurea at a mean (±SD) dose of 17.5±1.8 mg per kilogram per day. The retention rate was 94.2% at 3 years of treatment. Hydroxyurea therapy led to significant increases in both the hemoglobin and fetal hemoglobin levels. Dose-limiting toxic events regarding laboratory variables occurred in 5.1% of the participants, which was below the protocol-specified threshold for safety. During the treatment phase, 20.6 dose-limiting toxic effects per 100 patient-years occurred, as compared with 20.7 events per 100 patient-years before treatment. As compared with the pretreatment period, the rates of clinical adverse events decreased with hydroxyurea use, including rates of vaso-occlusive pain (98.3 vs. 44.6 events per 100 patient-years; incidence rate ratio, 0.45; 95% confidence interval [CI], 0.37 to 0.56), nonmalaria infection (142.5 vs. 90.0 events per 100 patient-years; incidence rate ratio, 0.62; 95% CI, 0.53 to 0.72), malaria (46.9 vs. 22.9 events per 100 patient-years; incidence rate ratio, 0.49; 95% CI, 0.37 to 0.66), transfusion (43.3 vs. 14.2 events per 100 patient-years; incidence rate ratio, 0.33; 95% CI, 0.23 to 0.47), and death (3.6 vs. 1.1 deaths per 100 patient-years; incidence rate ratio, 0.30; 95% CI, 0.10 to 0.88). CONCLUSIONS: Hydroxyurea treatment was feasible and safe in children with sickle cell anemia living in sub-Saharan Africa. Hydroxyurea use reduced the incidence of vaso-occlusive events, infections, malaria, transfusions, and death, which supports the need for wider access to treatment. (Funded by the National Heart, Lung, and Blood Institute and others; REACH ClinicalTrials.gov number, NCT01966731 .).


Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/administração & dosagem , Hidroxiureia/administração & dosagem , África ao Sul do Saara/epidemiologia , Anemia Falciforme/complicações , Anemia Falciforme/mortalidade , Antidrepanocíticos/efeitos adversos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Humanos , Hidroxiureia/efeitos adversos , Lactente , Malária/complicações , Malária/prevenção & controle , Doenças Negligenciadas/tratamento farmacológico , Dor/etiologia , Dor/prevenção & controle
7.
Am J Hematol ; 93(4): 537-545, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29318647

RESUMO

Despite its well-described safety and efficacy in the treatment of sickle cell anemia (SCA) in high-income settings, hydroxyurea remains largely unavailable in sub-Saharan Africa, where more than 75% of annual SCA births occur and many comorbidities exist. Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) is a prospective, Phase I/II open-label trial of hydroxyurea designed to evaluate the feasibility, safety, and benefits of hydroxyurea treatment for children with SCA in four sub-Saharan African countries. Following comprehensive training of local research teams, REACH was approved by local Ethics Committees and achieved full enrollment ahead of projections with 635 participants enrolled over a 30-month period, despite half of families living >12 km from their clinical site. At enrollment, study participants (age 5.4 ± 2.4 years) had substantial morbidity, including a history of vaso-occlusive pain (98%), transfusion (68%), malaria (85%), and stroke (6%). Significant differences in laboratory characteristics were noted across sites, with lower hemoglobin concentrations (P < .01) in Angola (7.2 ± 1.0 g/dL) and the DRC (7.0 ± 0.9 g/dL) compared to Kenya (7.4 ± 1.1 g/dL) and Uganda (7.5 ± 1.1 g/dL). Analysis of known genetic modifiers of SCA demonstrated a high frequency of α-thalassemia (58.4% with at least a single α-globin gene deletion) and G6PD deficiency (19.7% of males and 2.4% of females) across sites. The CAR ß-globin haplotype was present in 99% of participants. The full enrollment to REACH confirms the feasibility of conducting high-quality SCA research in Africa; this study will provide vital information to guide safe and effective dosing of hydroxyurea for children with SCA living in Africa.


Assuntos
Anemia Falciforme/tratamento farmacológico , Hidroxiureia/uso terapêutico , África ao Sul do Saara/epidemiologia , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Transfusão de Sangue , Criança , Pré-Escolar , Terapia Combinada , Comorbidade , Estudos de Viabilidade , Feminino , Saúde Global , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Humanos , Isquemia/etiologia , Malária/epidemiologia , Masculino , Estudos Prospectivos , Acidente Vascular Cerebral/etiologia , Talassemia alfa/epidemiologia
8.
Blood ; 130(24): 2585-2593, 2017 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-29051184

RESUMO

Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle-cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM (Novel use Of Hydroxyurea in an African Region with Malaria) was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2.5 mg/kg per day for 12 months. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events (AEs), clinical and laboratory effects, and hematological toxicities. Children received either hydroxyurea (N = 104) or placebo (N = 103). Malaria incidence did not differ between children on hydroxyurea (0.05 episodes per child per year; 95% confidence interval [0.02, 0.13]) vs placebo (0.07 episodes per child per year [0.03, 0.16]); the hydroxyurea/placebo malaria incidence rate ratio was 0.7 ([0.2, 2.7]; P = .61). Time to infection also did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%; P = .001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious AEs, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria). Hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or AEs. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined. This trial was registered at www.clinicaltrials.gov as #NCT01976416.


Assuntos
Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/epidemiologia , Hidroxiureia/uso terapêutico , Malária/epidemiologia , Anemia Falciforme/sangue , Antidrepanocíticos/uso terapêutico , Contagem de Células Sanguíneas , Pré-Escolar , Método Duplo-Cego , Doenças Endêmicas , Feminino , Hemoglobina Fetal/metabolismo , Humanos , Incidência , Lactente , Masculino , Estudos Prospectivos , Resultado do Tratamento , Uganda/epidemiologia
9.
JMIR Res Protoc ; 6(6): e107, 2017 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-28576754

RESUMO

BACKGROUND: In the Dominican Republic, where the burden of sickle cell anemia (SCA) is high, many children lack access to routine screening and preventative care. Children with SCA are at risk for stroke, an event that leads to significant morbidity and mortality. In the United States, screening via transcranial Doppler (TCD) identifies children with SCA at highest stroke risk, allowing early intervention with blood transfusions. The need for indefinite transfusions for primary stroke prevention limits their practicality in limited-resource countries. Hydroxyurea has been shown to lower TCD velocities and to prevent conversion from conditional (170 to 199 cm/sec) to abnormal (greater than or equal to 200 cm/sec) velocities. In resource-limited settings, implementation of a TCD screening program, coupled with hydroxyurea therapy, could reduce the burden of SCA and stroke. OBJECTIVE: The aims of the Stroke Avoidance for Children in REpública Dominicana (SACRED) trial are (1) to screen children with SCA for stroke risk using TCD and to determine the prevalence of elevated velocities in a cross-sectional sample; (2) to identify clinical and laboratory correlates of elevated velocities; and (3) to obtain longitudinal data on the natural history of TCD velocities and to measure therapeutic effects of hydroxyurea. METHODS: This prospective trial, designed and conducted by Cincinnati Children's Hospital Medical Center (CCHMC) and Hospital Infantil Robert Reid Cabral (HIRRC) with Centro de Obstetricia y Ginecología, includes a baseline cross-sectional epidemiological survey of the distribution of TCD velocities across a large cohort of children with SCA in the Dominican Republic. Children with conditional velocities are eligible to begin protocol-directed hydroxyurea if laboratory criteria are met. The treatment schedule begins with a fixed-dose of approximately 20 mg/kg/day for 6 months, after which it escalates to maximum tolerated dose (MTD). All participants undergo longitudinal annual TCD evaluation, while those on hydroxyurea have semi-annual evaluations during the 3-year study period. Data are collected using an Internet-based Research Electronic Data Capture (REDCap) system with forms translated into Spanish; both remote and on-site monitoring are used. RESULTS: To date, 122 children with SCA have enrolled in SACRED including 85 (69.7%, 85/122) with normal, 29 (23.8%, 29/122) with conditional, 5 (4.1%, 5/122) with abnormal, and 3 (2.5%, 3/122) with inadequate TCD velocities. Of the 29 children with conditional TCD velocities, 17 (59%, 17/29) have initiated hydroxyurea per protocol, with plans for escalation to MTD. CONCLUSIONS: The SACRED trial will provide novel epidemiologic data about the prevalence of children with SCA and increased stroke risk in the Dominican Republic. The study also includes an investigation of the impact of hydroxyurea at MTD on elevated TCD velocities, as well as clinical and laboratory parameters. The design and implementation of SACRED reflect a successful international institutional partnership, one that features local capacity building and training in research methods and clinical care. The trial's results have important implications for screening and prevention of primary stroke in children with SCA living in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02769845; https://www.clinicaltrials.gov/ct2/show/NCT02769845 (Archived by WebCite at http://www.webcitation.org/6qf6n0Egh).

10.
JMIR Res Protoc ; 5(3): e185, 2016 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-27619954

RESUMO

BACKGROUND: Cerebral vasculopathy in sickle cell anemia (SCA) begins in childhood and features intracranial arterial stenosis with high risk of ischemic stroke. Stroke risk can be reduced by transcranial doppler (TCD) screening and chronic transfusion therapy; however, this approach is impractical in many developing countries. Accumulating evidence supports the use of hydroxyurea for the prevention and treatment of cerebrovascular disease in children with SCA. Recently we reported that hydroxyurea significantly reduced the conversion from conditional TCD velocities to abnormal velocities; whether hydroxyurea can be used for children with newly diagnosed severe cerebrovascular disease in place of starting transfusion therapy remains unknown. OBJECTIVE: The primary objective of the EXpanding Treatment for Existing Neurological Disease (EXTEND) trial is to investigate the effect of open label hydroxyurea on the maximum time-averaged mean velocity (TAMV) after 18 months of treatment compared to the pre-treatment value. Secondary objectives include the effects of hydroxyurea on serial TCD velocities, the incidence of neurological and non-neurological events, quality of life (QOL), body composition and metabolism, toxicity and treatment response, changes to brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), genetic and serologic markers of disease severity, and cognitive and pulmonary function. METHODS: This prospective Phase II trial will enroll children with SCA in Jamaica, between the ages of 2 and 17 years, with either conditional (170-199 cm/sec) or abnormal (≥ 200 cm/sec) TCD velocities. Oral hydroxyurea will be administered daily and escalated to the maximum tolerated dose (MTD). Participants will be seen in the Sickle Cell Unit (SCU) in Kingston, Jamaica monthly until achieving MTD, and then every 3 months. TCD will be performed every 6 months. RESULTS: Currently, 43 participants have been enrolled out of a projected 50. There was one withdrawal due to immigration, with no permanent screen failures. Of the 43 enrolled, 37 participants have initiated study treatment. CONCLUSIONS: This trial investigates the effects of hydroxyurea treatment at MTD in children with conditional or abnormal TCD velocities before transfusion therapy and may represent an important advance towards establishing a suitable non-transfusion protocol for stroke prevention in children with SCA. The trial outcomes will have profound significance in developing countries where the disease burden is highest. CLINICALTRIAL: ClinicalTrials.gov NCT02556099; https://clinicaltrials.gov/ct2/show/NCT02556099 (Archived by WebCite at http://www.webcitation.org/6k1yMAa9G).

11.
JMIR Res Protoc ; 5(2): e110, 2016 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-27339303

RESUMO

BACKGROUND: Sickle cell anemia (SCA), one of most prevalent monogenic diseases worldwide, is caused by a glutamic acid to valine substitution on the beta globin protein of hemoglobin, which leads to hemolytic anemia. Hydroxyurea, the only disease-modifying therapy approved by the Food and Drug Administration for SCA, has proven to be a viable therapeutic option for SCA patients in resource-rich settings, given clinical improvements experienced while taking the medication and its once-daily oral dosing. Significant studies have demonstrated its safety and clinical efficacy among children and adults in developed countries. In Sub-Saharan Africa, however, the risk of malaria, hematologic toxicities, and safety of hydroxyurea in children with SCA living in malaria-endemic areas are unknown. OBJECTIVES: Study objectives include determining the incidence of malaria in SCA patients taking hydroxyurea versus placebo; establishing the frequency of hematologic toxicities and adverse events (AEs) in children with SCA treated with hydroxyurea versus placebo; and defining the relationships between hydroxyurea treatment and fetal hemoglobin, soluble intracellular adhesion molecule-1, and nitric oxide levels, and between levels of these factors and risk of subsequent malaria. METHODS: Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM, NCT01976416) is a prospective, randomized, placebo-controlled, double-blinded phase III trial to compare risk of malaria with oral hydroxyurea versus placebo. Children will be recruited from the Mulago Hospital Sickle Cell Clinic in Kampala, Uganda. RESULTS: Two hundred Ugandan children aged between 1.00 and 3.99 years with confirmed SCA will be randomized into treatment groups by order of entry in the study, based on a predetermined blinded randomization list. The primary outcome of the trial is malaria incidence in the 2 study groups, defined as episodes of clinical malaria occurring over the 1-year randomized study treatment period. CONCLUSION: NOHARM will be the first prospective randomized, placebo-controlled clinical trial investigating the use of hydroxyurea for children with SCA in a malaria-endemic region within Africa. The results of this trial have the potential to significantly advance understanding of how to safely and effectively use hydroxyurea in children with SCA in malaria-endemic areas. TRIAL REGISTRATION: Clinicaltrials.gov NCT01976416; https://clinicaltrials.gov/ct2/show/NCT01976416 (Archived by WebCite at http://www.webcitation.org/6hmoilZnp).

12.
Pediatr Blood Cancer ; 63(1): 98-104, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26275071

RESUMO

BACKGROUND: Sickle cell anemia (SCA) is an inherited hematological disorder that causes a large but neglected global health burden, particularly in Africa. Hydroxyurea represents the only available disease-modifying therapy for SCA, and has proven safety and efficacy in high-resource countries. In sub-Saharan Africa, there is minimal use of hydroxyurea, due to lack of data, absence of evidence-based guidelines, and inexperience among healthcare providers. PROCEDURE: A partnership was established between investigators in North America and sub-Saharan Africa, to develop a prospective multicenter research protocol designed to provide data on the safety, feasibility, and benefits of hydroxyurea for children with SCA. RESULTS: The Realizing Effectiveness Across Continents with Hydroxyurea (REACH, ClinicalTrials.gov NCT01966731) trial is a prospective, phase I/II open-label dose escalation study of hydroxyurea that will treat a total of 600 children age 1-10 years with SCA: 150 at each of four different clinical sites within sub-Saharan Africa (Angola, Democratic Republic of Congo, Kenya, and Uganda). The primary study endpoint will be severe hematological toxicities that occur during the fixed-dose treatment phase. REACH has an adaptive statistical design that allows for careful assessment of toxicities to accurately identify a safe hydroxyurea dose. CONCLUSIONS: REACH will provide data that address critical gaps in knowledge for the treatment of SCA in sub-Saharan Africa. By developing local expertise with the use of hydroxyurea and helping to establish treatment guidelines, the REACH trial results will have the potential to transform care for children with SCA in Africa.


Assuntos
Anemia Falciforme/tratamento farmacológico , Hidroxiureia/uso terapêutico , África ao Sul do Saara/epidemiologia , Anemia Falciforme/epidemiologia , Criança , Pré-Escolar , Humanos , Lactente , Estudos Prospectivos
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