Discussion board

Author (year) and country

Purpose

Study Design

Sample size and site

Treatment/ Intervention

Results

Implications for Nursing

Level of Evidence

Hasson et al., 2019. United States.

To evaluate the role of hydroxyurea in preventing silent strokes in SCD rather than chronic blood transfusions

Systematic review and meta-analysis

361 participants in observational study and 60 participants in RCT across the United States

The use hydroxyurea vs chronic blood transfusions in SCD patients to prevent stroke and silent stroke.

Findings suggest that hydroxyurea is safe and effective in preventing strokes. 

There was no difference between chronic blood transfusions and hydroxyurea for the outcome of treatment related adverse events.

Level I

Nevitt et al., 2017. United States and Belgium

To assess the effects of hydroxyurea therapy in people with SCD (all genotypes), of any age, regardless of setting.

Systematic review

Eight randomized controlled trials of one month or longer, with a total of 899 children and adults with sickle cell disease (SCD)

Reviewing and comparing data collection from eight randomized controlled trials on the use of hydroxyurea in contrast to placebo, standard therapy or other interventions for people with SCD.

Throughout the studies the groups using Hydroxyurea had a decrease in pain crises, blood transfusions, hospitalizations, hemolytic factor (p<0.001), and increase in hemoglobin and fetal hemoglobin (p<0.001) 

Hydroxyurea has been proven to benefit patients with Sickle Cell Disease and in order to ensure proper use of Hydroxyurea and to maximize its benefits and safety there should be an established prescribing and monitoring protocol. 

Level I

Meier et al., 2020. USA.

To Validating viability and benefits of pharmacokinetics-guided dosing approach

Randomized controlled trials

116 patients aged from 6 to 2 years across the United States recruited from pediatric sickle cell centers 

20mg/kg/day of hydroxyurea

Or individualized PK-guided dose. After initiation, a reduction or increase of hydroxyurea protocol based on study design. 

Early initiation of hydroxyurea using individualized PK- guided dosing has the potential to be close to a curative therapy. Reduction in clinical complications. High levels and pan cellular expression of HbF within red blood cells.

Improved laboratory response 

Monitoring of HbF and the determinants of maximum hydroxyurea induced HbF responses. 

Collection of study data and biospecimen

Level II

Ofakunrin et al., 2020. Nigeria.

Show effectiveness and safety of hydroxyurea in the treatment of Sickle Cell Anemia in Nigeria 

Quazi-experimental study

54 SCA Children 4-17 yrs. old in Nigeria

Hydroxyurea was started at 20mg/kg and increased by 5mg/kg every 8 weeks to a maximum dose of 35mg/kg and treated up to 12 months. 

The number of patients with more than two pain crises reduced from 27 to 2. Acute chest syndrome reduced from 6 to 0. The risk of being transfused more than once decreased.

Safety of hydroxyurea was assessed by monitoring hematologic toxicity and adverse clinical events during therapy. Hematologic toxicity was present if HCT level was <15% (severe anemia), leucopenia, or thrombocytopenia

Level II

et al., Tshilolo et al., 2019. Sub-Saharan Africa

The purpose of the study is to investigate the feasibility, safety, and benefits of using Hydroxyurea for children with sickle cell anemia when it is coexisting with other conditions such as malaria and malnutrition. 

Randomization

The study used children between the age of 1 to 10 years. Out of the 635 children that were fully enrolled, 606 completed the screening process and began receiving hydroxyurea. The healthcare facilities that were used in the study included

“Hospital”. 

The study participants were administered with a median of 18 mg per kilogram. It was within the range of 15 to 20 mg per kg. The study participants were administered the dosage for 6 months. After that, the dose. 

From the study, it was identified that the retention rate of the drug was 94.2% in the next three months. The study indicated that the administration of hydroxyurea led to a significant increase in fetal hemoglobin.

There was a significant reduction in the incidence of all the clinical adverse events between the screening and the treatment phases during hydroxyurea treatment. The overall rate of sickle cell anemia was reduced significantly at 114.5 events per 100 patient-years compared to 53.0 events per 100 

Level II

Lori et al., 2016. United States

To determine safety of Hydroxyurea for the treatment of HbSC disease in pediatric and adult patients. 

Quasi experimental study  

133 adult and pediatric HbSC patients receiving Hydroxyurea at 18 sickle cell centers across the United States 

Administering Hydroxyurea to children and adults with HbSC, typically for treatment of recurrent vaso-occlusive 

pain.   

38% reduction of vaso-occlusive pain events after 12 months of hydroxyurea therapy  

Although Hydroxyurea has proven to be efficacious, safe, and cost effective for the treatment of HbSS, it has not yet been approved in the treatment of HbSC. 

Level III

Quarmyne et al., 2017. United States

To evaluate the clinical effectiveness of Hydroxyurea treatment in the pediatric population

Retrospective cohort study 

134 children with sickle cell anemia at the Children’s Healthcare of Atlanta treated with Hydroxyurea from 2009-2011 

Recording clinical information before Hydroxyurea initiation and at least three months after treatment. 

Significant decrease in healthcare utilization post Hydroxyurea treatment with a decline in emergency room visits, pain encounters, acute chest syndrome, and blood transfusions.     

Hydroxyurea has proven to be clinically effective in the treatment of sickle cell anemia in children and should be prescribed to decrease hospitalization and impatient days.

Level V

Aikhionbare et al., 2019. Nigeria

To raise awareness of the potential use of Hydroxyurea in children with Sickle Cell Disease since its use is yet not a standard of care in Africa where the burden of SCD is high and to discuss the outcome of children with sickle cell disease after a minimum of 6 months of Hydroxyurea therapy.

Retrospective review

537 children aged 2-16 years over a 4-year period from January 2010 to January 2014. During the period 74 children of the 537 were treated with Hydroxyurea 

Hydroxyurea was given to 74 children, it was started at 15 mg/kg daily single dose, increasing to a maximum of 30 mg/kg. Follow-ups and full clinical evaluations were done regularly. Specific questions relating to the potential side-effects of HU were asked and specific blood tests were done before treatment was started at each follow-up visit and/or as required by the physician.

Hydroxyurea therapy was shown to significantly decrease the rates of severe complications of SCD such as vaso-occlusive crisis, repeated blood transfusions, hospital admissions and sequestration crises (p<0.05).

Hydroxyurea therapy appears to be beneficial in children with SCD in this study setting, with improvements in clinical events and minimal side-effects from treatment. The use of Hydroxyurea should be established as the standard of care for children with SCD in Africa. 

Level V

Karkoska et al., 2021. United States

To review the hydroxyurea-prescribing practices within the Comprehensive Sickle Cell Clinic over the period    2010–2019 comparing the periods before and after the release of the 2014 NHLBI guidelines.

Retrospective review/Randomized and quasi‐randomized controlled trials

439 patients followed for at least 1 year at Comprehensive Sickle Cell Center at the Cincinnati Children's Hospital Medical Center

from 2010 to 2019 

Retrospective review, data collection and study of the hydroxyurea-prescribing practices and associated clinical outcomes at the Comprehensive Sickle Cell Center before and after the 2014 National Heart, Lung, and Blood Institute (NHLBI) recommendations to use hydroxyurea for all children with sickle cell anemia

Hydroxyurea use was increased within the pediatric population studied from 43% in 2010 to 95% in 2019.The age of hydroxyurea initiation was significantly younger during 2014–2019 compared to 2010–2013. 97% of children born after 2013 received disease-modifying therapy (Hydroxyurea) by the end of 2019. All of these new practices lead to a decrease of hospitalizations related to sickle cell anemia from 67/100 patient-years in 2010 to 39/100 patient-years in 2019 (p < .001)

This study demonstrated that careful and deliberate commitment to follow the NHLBI guidelines to initiate early and universal prescription of hydroxyurea for children with sickle cell disease, result on improvements in clinical and patient outcomes

Level V

Chambers et al., 2018. Cabinda province, Angola. 

To determine if SCD patients in a resource- limited area in Angola, regardless of clinical severity, benefited from a fixed intermittent dose of hydroxyurea for at least 6 months.

Retrospective Study

303 patients at The Angola Sickle Cell Initiative in the Cabinda province. 

Patients received a uniform dose of 20mg/kg/day

of hydroxyurea. Because only the 500mg capsule was available, the dose was averaged weekly. Because of this, some children received uneven daily doses or were instructed to skip medicine on some days.

The study showed beneficial outcomes in patients with SCD treated with intermittent or uneven daily dosing of hydroxyurea is as effective as fixed daily doses. This is significant because only generic 500mg capsules are available or affordable in Sub-Saharan Africa.  

There were no differences in magnitude of hydroxyurea-induced changes between patients prescribed intermittent or uneven doses and uniform daily doses 

Level V