Hydroxyurea to Prevent Organ Damage in Children with Sickle Cell Anemia (BABY HUG) Phase III Clinical Trial and Follow-Up Observational Studies I and II
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PROVIDER: PRJNA726594 | ENA |
REPOSITORIES: ENA
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Project description:Hydroxyurea to Prevent Organ Damage in Children with Sickle Cell Anemia (BABY HUG) Phase III Clinical Trial and Follow-Up Observational Studies I and II
| PRJNA726593 | ENA
Project description:We hypothesized that miRNA regulation may be invloved in hydroxyurea-mediated fetal hemoglobin induction. Microarray analysis was utilized as an initial screening tool to determine differential miRNA expression in CD71+ erythroid cells comparing cells from control individuals without sickle cell anemia to patients with sickle cell anemia prior to treatment with hydroxyurea and patients receiving the maximum tolerated dose (MTD) of hydroxurea. CD71+ cells were isolated from whole blood of control individuals (n=2), pediatric patients without hydroxyurea treatment (n=3) and pediatric patients at hydroxyurea MTD (n=3). All 8 samples were analyzed for miRNA expression.
2011-11-21 | E-GEOD-32035 | biostudies-arrayexpress
Project description:We hypothesized that miRNA regulation may be invloved in hydroxyurea-mediated fetal hemoglobin induction. Microarray analysis was utilized as an initial screening tool to determine differential miRNA expression in CD71+ erythroid cells comparing cells from control individuals without sickle cell anemia to patients with sickle cell anemia prior to treatment with hydroxyurea and patients receiving the maximum tolerated dose (MTD) of hydroxurea.
2011-11-21 | GSE32035 | GEO
Project description:Sickle cell anemia (SCA) is a severe, inherited hemoglobin disorder affecting 100,000 persons in the US and millions worldwide. Hydroxyurea, a once daily oral medication, has emerged as the primary disease-modifying therapy for SCA. The accumulated body of evidence over 30 years demonstrates that hydroxyurea is a safe and effective therapy for SCA, but hydroxyurea remains underutilized for a variety of reasons.In this review, we summarize the available evidence regarding the pharmacology, clinical, and laboratory benefits, and safety of hydroxyurea therapy for the treatment of SCA. The purpose of this review is to provide the reader a comprehensive understanding of hydroxyurea and to reinforce the fact that hydroxyurea is a safe and effective medication for the treatment of SCA.In our opinion, hydroxyurea therapy should be considered standard-of-care for SCA, representing an essential component of patient management. Early initiation and broader use of hydroxyurea will alter the natural history of SCA, so affected children can live longer and healthier lives. In addition, hydroxyurea use should be extended to low-resource settings such as sub-Saharan Africa, where the burden of SCA and the need for hydroxyurea is arguably the greatest.
| S-EPMC5868345 | biostudies-literature
Project description:Background and objectiveSusceptibility to encapsulated bacteria is well known in sickle cell disease (SCD). Hydroxyurea use is common in adults and children with SCD, but little is known about hydroxyurea's effects on immune function in SCD. Because hydroxyurea inhibits ribonucleotide reductase, causing cell cycle arrest at the G1-S interface, we postulated that hydroxyurea might delay transition from naive to memory T cells, with inhibition of immunologic maturation and vaccine responses.MethodsT-cell subsets, naive and memory T cells, and antibody responses to pneumococcal and measles, mumps, and rubella vaccines were measured among participants in a multicenter, randomized, double-blind, placebo-controlled trial of hydroxyurea in infants and young children with SCD (BABY HUG).ResultsCompared with placebo, hydroxyurea treatment resulted in significantly lower total lymphocyte, CD4, and memory T-cell counts; however, these numbers were still within the range of historical healthy controls. Antibody responses to pneumococcal vaccination were not affected, but a delay in achieving protective measles antibody levels occurred in the hydroxyurea group. Antibody levels to measles, mumps, and rubella showed no differences between groups at exit, indicating that effective immunization can be achieved despite hydroxyurea use.ConclusionsHydroxyurea does not appear to have significant deleterious effects on the immune function of infants and children with SCD. Additional assessments of lymphocyte parameters of hydroxyurea-treated children may be warranted. No changes in current immunization schedules are recommended; however, for endemic disease or epidemics, adherence to accelerated immunization schedules for the measles, mumps, and rubella vaccine should be reinforced.
| S-EPMC4179098 | biostudies-literature
Project description:The laboratory and clinical benefits of hydroxyurea therapy for children with sickle cell anemia (SCA) are well recognized, but treatment in young patients is limited in part by concerns about long-term genotoxicity, and specifically possible carcinogenicity.The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) was a multicenter double-blinded placebo-controlled randomized clinical trial (NCT00006400) testing whether hydroxyurea could prevent chronic organ damage in very young patients with SCA. An important secondary objective was the measurement of acquired genotoxicity using three laboratory assays: chromosomal karyotype, illegitimate VDJ recombination events, and micronucleated reticulocyte formation.Our data indicate that hydroxyurea treatment was not associated with any significant increases in genotoxicity compared to placebo treatment.These data provide additional support to the safety profile of hydroxyurea for young patients with SCA, and suggest that genotoxicity in this patient population is low.
| S-EPMC3277805 | biostudies-literature
Project description:The Multicenter Study of Hydroxyurea (HU) in Sickle Cell Anemia (MSH) previously showed that daily oral HU reduces painful sickle cell (SS) crises by 50% in patients with moderate to severe disease. The morbidity associated with this disease is known to have serious negative impact on the overall quality of life(QOL) of affected individuals.The data in this report were collected from the 299 patients enrolled in the MSH. Health quality of llife (HQOL) measures were assessed in the MSH as a secondary endpoint to determine if the clinical benefit of HU could translate into a measurable benefit perceptible to the patients. HQOL was assessed with the Profile of Mood States, the Health Status Short Form 36 (SF-36), including 4-week pain recall, and the Ladder of Life, self-administered twice 2-weeks apart pre-treatment and every 6 months during the two-year, randomized, double-blind, treatment phase. The effects of factors including randomized treatment, age, gender, pre-treatment crises frequency, Hb-F level mean, daily pain from 4-week pre-treatment diaries, and 2-year Hb-F response level (low or high) were investigated.Over two years of treatment, the benefit of HU treatment on QOL, other than pain scales, was limited to those patients taking HU who maintained a high HbF response, compared to those with low HbF response or on placebo. These restricted benefits occurred in social function, pain recall and general health perception. Stratification according to average daily pain prior to treatment showed that responders to HU whose average daily pain score was 5-9 (substantial pain) achieved significant reduction in the tension scale compared to the placebo group and to non-responders. HU had no apparent effect on other QOL measures.Treatment of SS with HU improves some aspects of QOL in adult patients who already suffer from moderate-to-severe SS.
| S-EPMC1569824 | biostudies-other
Project description: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 .).
| S-EPMC6454575 | biostudies-literature
Project description:OBJECTIVE:To evaluate the impact of an initiative to increase hydroxyurea use among children with sickle cell anemia (SCA) who presented to the emergency department (ED). STUDY DESIGN:This observational cohort study included children with SCA not taking hydroxyurea who presented to the ED with pain or acute chest syndrome and then attended a Quick-Start Hydroxyurea Initiation Project (Q-SHIP) session. A Q-SHIP session includes a hematologist-led discussion on hydroxyurea, a video of patients talking about hydroxyurea, and a direct offer to start hydroxyurea. RESULTS:Over 64 weeks, 112 eligible patients presented to the ED and 59% (n?=?66) participated in a Q-SHIP session a median of 6 days (IQR 2, 20 days) after ED or hospital discharge; 55% of participants (n?=?36) started hydroxyurea. After a median follow-up of 49 weeks, 83% (n?=?30) of these participants continued hydroxyurea. Laboratory markers of hydroxyurea adherence were significantly increased from baseline: median mean corpuscular volume +8.6?fL (IQR 5.0, 17.7, P?<?.0001) and median hemoglobin F +5.7% (IQR 2.5, 9.8, P?=?.0001). Comparing Q-SHIP participants to nonparticipants, 12 weeks after ED visit, participants were more likely to have started hydroxyurea than nonparticipants (53% vs 20%, P?=?.0004) and to be taking hydroxyurea at last follow-up (50% vs 20%, P?=?.001). Two years after the implementation of Q-SHIP the overall proportion of eligible patients on hydroxyurea presenting to our ED increased from 56% to 80%, P?=?.0069. CONCLUSIONS:Participation in a clinic to specifically address starting hydroxyurea after a SCA complication increases hydroxyurea use.
| S-EPMC6159227 | biostudies-literature
Project description:Hydroxyurea has many characteristics of an ideal drug for sickle cell anemia (SCA) and provides therapeutic benefit through multiple mechanisms of action. Over the past 25 years, substantial experience has accumulated regarding its safety and efficacy for patients with SCA. Early proof-of-principle studies were followed by prospective phase 1/2 trials demonstrating efficacy in affected adults, then adolescents and children, and more recently infants and toddlers. The phase 3 National Heart, Lung and Blood Institute-sponsored Multicenter Study of Hydroxyurea trial proved clinical efficacy for preventing acute vaso-occlusive events in severely affected adults. Based on this cumulative experience, hydroxyurea has emerged as an important therapeutic option for children and adolescents with recurrent vaso-occlusive events; recent evidence documents sustained long-term benefits with prevention or reversal of chronic organ damage. Despite abundant evidence for its efficacy, however, hydroxyurea has not yet translated into effective therapy for SCA. Because many healthcare providers have inadequate knowledge about hydroxyurea, patients and families are not offered treatment or decline because of unrealistic fears. Limited support for hydroxyurea by lay organizations and inconsistent medical delivery systems also contribute to underuse. Although questions remain regarding its long-term risks and benefits, current evidence suggests that many young patients with SCA should receive hydroxyurea treatment.
| S-EPMC2902131 | biostudies-literature