Browsing by Subject "Hydroxyurea"
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Item Open Access Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial.(Lancet, 2016-02-13) Ware, Russell E; Davis, Barry R; Schultz, William H; Brown, R Clark; Aygun, Banu; Sarnaik, Sharada; Odame, Isaac; Fuh, Beng; George, Alex; Owen, William; Luchtman-Jones, Lori; Rogers, Zora R; Hilliard, Lee; Gauger, Cynthia; Piccone, Connie; Lee, Margaret T; Kwiatkowski, Janet L; Jackson, Sherron; Miller, Scott T; Roberts, Carla; Heeney, Matthew M; Kalfa, Theodosia A; Nelson, Stephen; Imran, Hamayun; Nottage, Kerri; Alvarez, Ofelia; Rhodes, Melissa; Thompson, Alexis A; Rothman, Jennifer A; Helton, Kathleen J; Roberts, Donna; Coleman, Jamie; Bonner, Melanie J; Kutlar, Abdullah; Patel, Niren; Wood, John; Piller, Linda; Wei, Peng; Luden, Judy; Mortier, Nicole A; Stuber, Susan E; Luban, Naomi LC; Cohen, Alan R; Pressel, Sara; Adams, Robert JBACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (≥ 200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01425307. FINDINGS: Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140-146) in children who received standard transfusions and 138 cm/s (135-142) in those who received hydroxycarbamide, with a difference of 4·54 (0·10-8·98). Non-inferiority (p=8·82 × 10(-16)) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five [8%] patients with hydroxycarbamide and three events in one [2%] patient for transfusions). INTERPRETATION: For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke. FUNDING: National Heart, Lung, and Blood Institute, National Institutes of Health.Item Open Access Hydroxyurea use and Plasmodium falciparum prevalence among children with sickle cell anemia in Homa Bay, Kenya; a cross sectional study(2019) Nantume, Assumpta SolomeHydroxyurea, a mainstay of sickle cell management in the developed world, offers a range of potential benefits to children with sickle cell disease. There is strong evidence that hydroxyurea induces production of fetal hemoglobin (HbF) in red blood cells, which is generally associated with reduced morbidity and fewer incidents of clinical events in sickle cell patients. Based on literature from in vitro investigations, it has also been suggested that hydroxyurea may confer some protection against malaria parasitemia by inhibiting proliferation of the malaria-causing parasite - Plasmodium falciparum.
The purpose of this study was to examine the effects hydroxyurea use on P. falciparum infection, parasite density, HbF and morbidity among children with sickle cell disease living in a malaria endemic setting. We analyzed baseline data of 95 children (aged 1 – 10 years) enrolled in the EPiTOMISE clinical trial (Enhancing Preventive Therapy of Malaria in children with Sickle cell anemia in East Africa) between January 2018 and September 2018.
Our analyses showed no significant difference in the prevalence of P. falciparum infection between hydroxyurea users and non-hydroxyurea users, prevalence ratio [95% CI] = 1.14 [0.76, 1.71]. Among infected children, median (IQR) log parasites densities were also similar between hydroxyurea users, -0.96 (-1.67, 0.41) and hydroxyurea non-users, -0.12 (-1.32, 3.48), p-value=0.146.
We did observe substantial hematological benefits among hydroxyurea users including an approximate 1 unit increase in median hemoglobin concentration and a 2.7-fold increase in median percentage HbF. However, this observation did not translate to any meaningful difference in the prevalence of morbidity events.
In agreement with the few studies on hydroxyurea use in malaria endemic settings, these results suggest that there may be no added risk of P. falciparum infection to sickle cell patients who routinely use hydroxyurea. Furthermore, our results reflect that hydroxyurea use is associated with increased HbF and a better hematological profile in this population. There is need for more research on hydroxyurea use in sub-Saharan Africa to help resolve any existing concerns and conflicting data in the current body of literature.
Item Open Access Is low dose hydroxyurea the solution to the global epidemic of sickle cell disease?(Pediatr Blood Cancer, 2015-06) Strouse, John JItem Open Access What does it mean to be affiliated with care?: Delphi consensus on the definition of "unaffiliation" and "specialist" in sickle cell disease.(PloS one, 2022-01) Lamont, Andrea E; Hsu, Lewis L; Jacobs, Sara; Gibson, Robert; Treadwell, Marsha; Chen, Yumei; Lottenberg, Richard; Axelrod, Kathleen; Varughese, Taniya; Melvin, Cathy; Smith, Sharon; Chukwudozie, Ifeanyi Beverly; Kanter, Julie; Sickle Cell Disease Implementation ConsortiumAccruing evidence reveals best practices for how to help individuals living with Sickle Cell Disease (SCD); yet, the implementation of these evidence-based practices in healthcare settings is lacking. The Sickle Cell Disease Implementation Consortium (SCDIC) is a national consortium that uses implementation science to identify and address barriers to care in SCD. The SCDIC seeks to understand how and why patients become unaffiliated from care and determine strategies to identify and connect patients to care. A challenge, however, is the lack of agreed-upon definition for what it means to be unaffiliated and what it means to be a "SCD expert provider". In this study, we conducted a Delphi process to obtain expert consensus on what it means to be an "unaffiliated patient" with SCD and to define an "SCD specialist," as no standard definition is available. Twenty-eight SCD experts participated in three rounds of questions. Consensus was defined as 80% or more of respondents agreeing. Experts reached consensus that an individual with SCD who is unaffiliated from care is "someone who has not been seen by a sickle cell specialist in at least a year." A sickle cell specialist was defined as someone with knowledge and experience in SCD. Having "knowledge" means: being knowledgeable of the 2014 NIH Guidelines, "Evidence-Based Management of SCD", trained in hydroxyurea management and transfusions, trained on screening for organ damage in SCD, trained in pain management and on SCD emergencies, and is aware of psychosocial and cognitive issues in SCD. Experiences that are expected of a SCD specialist include experience working with SCD patients, mentored by a SCD specialist, regular attendance at SCD conferences, and obtains continuing medical education on SCD every 2 years." The results have strong implications for future research, practice, and policy related to SCD by helping to lay a foundation for an new area of research (e.g., to identify subpopulations of unaffiliation and targeted interventions) and policies that support reaffiliation and increase accessibility to quality care.