scholarly journals Pain and other non-neurological adverse events in children with sickle cell anemia and previous stroke who received hydroxyurea and phlebotomy or chronic transfusions and chelation: Results from the SWiTCH clinical trial

2013 ◽  
Vol 88 (11) ◽  
pp. 932-938 ◽  
Author(s):  
Ofelia Alvarez ◽  
Nancy A. Yovetich ◽  
J. Paul Scott ◽  
William Owen ◽  
Scott T. Miller ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Previous Stroke

scholarly journals Randomization is not associated with socio-economic and demographic factors in a multi-center clinical trial of children with sickle cell anemia

2014 ◽  
Vol 61 (9) ◽  
pp. 1529-1535 ◽  
Author(s):  
Dionna O. Roberts ◽  
Brittany Covert ◽  
Mark J. Rodeghier ◽  
Nagina Parmar ◽  
Michael R. DeBaun ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Demographic Factors

A Randomized Trial of the Safety and Benefit of Transfusion Vs. Standard Care In the Prevention of Sickle Cell-Related Complications In Adults: a Preliminary Report From the Phase II NHLBI Comprehensive Sickle Cell Centers (CSCC) Study of Neuropsychological Dysfunction and Neuroimaging Abnormalities In Neurologically Intact Adult Patients with Sickle Cell Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3221-3221 ◽  
Author(s):  
Elliott Vichinsky ◽  
Lynne Neumayr ◽  
Jeffrey I Gold ◽  
Michael W Weiner ◽  
Jeffrey Kasten ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Adverse Events ◽  
Randomized Trial ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Preliminary Report ◽  
Standard Care ◽  
Neurocognitive Function ◽  
Cell Disease ◽  
Transfusion Therapy

Abstract Abstract 3221 Background: Most adult sickle cell anemia patients have received transfusion therapy. However, prospective studies evaluating the efficacy of transfusions in preventing sickle cell-related complications are lacking. The Phase II Neuropsychological Adult Sickle Cell Anemia Study is a randomized trial of chronic transfusion vs. standard of care in patients with abnormal neurocognitive function in order to determine the safety and benefits of transfusion therapy on neurocognitive function. A secondary goal of the study is to evaluate the benefit of chronic transfusion on the frequency and severity of acute sickle cell events; this is a preliminary report of this specific aim. Methods: Eligibility required normal neurological exam, WAIS III PIQ score ≤ 90, hemoglobin ≤ 9 g/dL, hemoglobin SS electrophoresis, and age between 21 and 55 years. Patients were randomly assigned to receive either standard care or transfusions. The transfusion goal was to maintain a hemoglobin of 2 g/dL rise over baseline with matched red cells for D, C/c, E/e, and Kell antigens. The protocol required simple transfusions at approximately 4 week intervals. Chelation therapy was not part of the study design. Patients underwent serial clinical and laboratory evaluations with central analysis of all clinical and transfusion events and complications. Laboratory testing of subjects in the transfusion arm included quantitative hemoglobin S/A, hemoglobin concentration, ferritin levels, and red cell antibody screening; a full hematology/chemistry panel was performed for all subjects at baseline, the study mid-point, and at the end of the study. Results: There were 20 patients in the transfusion arm (TX arm) with a mean age of 29 years vs. 16 patients in the standard care arm (SC arm) with a mean age of 30.5 years. The baseline data in the TX arm was similar to the SC arm: hemoglobin 7.8 vs. 8.0 g/dL; hematocrit 22.6% vs. 23.1%; hemoglobin F 10.5% vs. 12.5%. Thirty-five percent of patients randomized to the TX arm had a history of acute chest syndrome (ACS) vs. 31% in the SC arm; 30% of patients in the TX arm were on hydroxyurea compared to 50% in the SC arm. The TX arm patients have received an average of 5.6 transfusions (2 units per transfusion) with only one subject requiring an acute transfusion (5%); in contrast, 4 SC arm patients (25%) were transfused for acute events for a total of 7 units (average 1.8 per patient). The transfusion therapy improved the average hematologic status of patients: hemoglobin S% decreased from 85% to 32% (p=0.0003); hemoglobin and hematocrit increased from 7.6 to 9.4 g/dL (p=0.0052) and 22% to 28%, (p=0.007), respectively. Bilirubin declined from 3.6 to 2.4 mg/dL (p=0.042). In contrast, only bilirubin showed a significant decrease in the SC arm. In the TX arm, serum ferritin rose an average of 1318 to 2368 (p=.001); there was no change in liver function. There were no clinical transfusion reactions in the 120 study transfusions (360 units); however, one patient on routine screening reported a transient anti-D antibody without clinical or laboratory changes. Clinical Results: Adverse events were higher in the SC arm. Total number of adverse events in the TX arm were 23 (1.2 per person) vs. 66 in (4.1 per person) in the SC arm. There were 5 hospitalizations in the TX arm and 21 in the SC care arm, with a median number of hospitalized days per hospitalization of 5.0 and 6.0 respectively. The total number of serious events was 6 in the TX arm (0.3 per person) vs. 23 in the SC arm (1.4 per person). The total number of vaso-occlusive events in the TX arm were 14 (0.7 per person) vs. 57 (3.6 per person) in the SC arm. Acute pulmonary events occurred in 25% (4 patients) of the SC arm vs. none in the TX arm. Conclusions: This is preliminary data from the first prospective randomized study of the safety and efficacy of transfusion therapy in adults with SCD. We demonstrate the safety of transfusion therapy. Compared to standard therapy, transfusions improve or stabilize critical laboratory markers, decrease serious sickle cell anemia-related adverse events, and decrease in hospitalizations. Increase in ferritin is an expected outcome in transfused patients since chelation was not a part of this transfusion protocol. On completion of the study, the potential benefits of transfusion therapy on sickle cell disease morbidity including neurocognitive function will be reported. Disclosures: Field: Novartis Pharm: Honoraria.

scholarly journals Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial

2015 ◽  
Vol 90 (12) ◽  
pp. 1099-1105 ◽  
Author(s):  
Jane S. Hankins ◽  
Mary Beth McCarville ◽  
Angela Rankine-Mullings ◽  
Marvin E. Reid ◽  
Clarisse L.C. Lobo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Randomized Clinical Trial ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Transcranial Doppler ◽  
Phase Iii

Therapeutic Phlebotomy in Children with Sickle Cell Anemia, Stroke, and Iron Overload: The SWiTCH Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1044-1044 ◽  
Author(s):  
Banu Aygun ◽  
Nicole A Mortier ◽  
Karen Kesler ◽  
Willliam H Schultz ◽  
Ofelia A. Alvarez ◽  
...  
Keyword(s):  
Adverse Events ◽  
Iron Overload ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Recurrent Stroke ◽  
Venous Access ◽  
Study Entry ◽  
Liver Iron ◽  
History Of ◽  
The Mean

Abstract Abstract 1044 Background: Stroke With Transfusions Changing to Hydroxyurea (SWiTCH Clinical Trials.gov NCT00122980), an NHLBI-sponsored Phase III multicenter trial, compared chronic blood transfusions/chelation to hydroxyurea/phlebotomy for the reduction of recurrent stroke and improvement in iron overload management in children with sickle cell anemia (SCA) and history of overt stroke. To date, however, phlebotomy to manage iron overload has not been commonly performed in children, especially those with SCA. Objective: To describe the experience with SWiTCH phlebotomy procedures, including success rate, associated adverse events, and effect on liver iron stores. Methods: Quantitative liver iron concentration (LIC) was measured by liver biopsy at study entry. Only subjects with LIC > 5 mg Fe/gram dry weight liver (DWL) were eligible for randomization. Those randomized to hydroxyurea/phlebotomy received decreasing volumes of monthly transfusion during hydroxyurea dose escalation, which lasted 4–9 months. Phlebotomy was performed every 4±1 weeks after discontinuation of transfusions. The prescribed phlebotomy volume was 10 mL/kg (maximum 500 mL) for Hb ≥ 8.0 gm/dL, and 5 mL/kg for Hb 7.0–7.9 gm/dL. Phlebotomy was held if Hb was <7.0 gm/dL. Phlebotomy was performed over 30 minutes with immediate normal saline replacement, typically using peripheral venous access. Exit LIC by liver biopsy was obtained in those completing 30 months of therapy. Ferritin was monitored monthly in all subjects using a centralized laboratory. Results: Sixty-seven children (mean age 13.0 ± 4.0 years; range 5.2–19.0 years) with history of previous stroke and transfusion therapy for an average of 7.4 ± 3.8 years (range 1.5–15.5 years) were randomized to the hydroxyurea/phlebotomy arm. Most of them had also received chelation therapy: 47 (71%) with deferoxamine for an average of 4.8 ± 3.2 years, and 57 (86%) with deferasirox for 1.5 ± 0.8 years prior to study entry. Their average entry LIC was 16.5 ± 9.4 mg/gram DWL. Sixty of 67 children (90%) successfully transitioned to hydroxyurea after 7.2 ± 2.4 months of transfusion overlap; one subject had a stroke during overlap and six failed to demonstrate adequate response/compliance to hydroxyurea to safely discontinue transfusions. These 60 subjects received an average of 8 ± 3 transfusions providing 63 ± 44 mL/kg PRBCs before completing transition and commencing phlebotomy, and 3 ± 3 transfusions providing 19 ± 20 mL/kg PRBCs after starting phlebotomy, for various clinical indications. During the course of the study, a total of 935 phlebotomies were performed (mean 16 per subject) removing an average total volume of 127 ± 74 mL/kg per subject. The mean pre-phlebotomy Hb level on hydroxyurea (9.1 gm/dL) was not significantly different than the mean pre-transfusion Hb during the transfusion overlap period (9.0 gm/dL). Mean ferritin for these 60 subjects on the hydroxyurea/phlebotomy arm decreased from 3523 ± 2150 ng/mL at study entry to 2227 ± 1646 ng/mL (p<0.0001) at exit; and decreased in 50 of 60 subjects. For the 23 patients on the hydroxyurea/phlebotomy arm who completed 30 months of study treatment, the average LIC was unchanged (18.5 mg Fe/gram DWL at entry compared to 18.1 mg Fe/gram at exit, p=0.817). However, average ferritin level for these subjects was significantly lower at exit (4216 ± 2799 ng/mL vs 2356 ± 2032 ng/mL, respectively, p=0.0003). Of 968 protocol-directed phlebotomy procedures, 935 (97%) were performed; 94% of which were at full prescribed volume. Of the 33 phlebotomy procedures that were not performed, 11 were held due to Hb < 7.0 gm/dL and 9 due to poor venous access. There were only 33 grade 2 adverse events (3.5% prevalence) reported in 12 subjects and no serious adverse events. The most common complication was hypotension (9 events; 5 subjects) followed by dizziness, syncope, headache and weakness. Six subjects had a recurrent stroke but there was no temporal relationship to the phlebotomy procedures. Conclusions: Therapeutic phlebotomies were well-tolerated and did not result in worsening anemia or stroke recurrence in this cohort of children with SCA and previous stroke switched to hydroxyurea. Although ferritin levels decreased significantly, we did not demonstrate an overall decrease in LIC in this heavily iron overloaded cohort, most likely due to continued iron loading with transfusions in the overlap period and subsequent short duration of phlebotomy. Disclosures: Off Label Use: Use of hydroxyurea in children with sickle cell anemia.

Perceived benefits and risks of participation in a clinical trial for Ugandan children with sickle cell anemia

2019 ◽  
Vol 67 (2) ◽  
Author(s):  
Aubri S. Carman ◽  
Casey Sautter ◽  
Juliana N. Anyanwu ◽  
Andrew S. Ssemata ◽  
Robert O. Opoka ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Perceived Benefits

scholarly journals Zinc for Infection Prevention in Sickle Cell Anemia (ZIPS): Study Protocol for a Randomized Placebo-Controlled Trial in Ugandan children with Sickle Cell Anemia

2019 ◽  
Author(s):  
Dibyadyuti Datta ◽  
Ruth Namazzi ◽  
Andrea L. Conroy ◽  
Sarah E. Cusick ◽  
Heather A. Hume ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Zinc Supplementation ◽  
Controlled Trial ◽  
Sub Saharan Africa ◽  
Invasive Infection ◽  
Risk Of Infection ◽  
African Children ◽  
Increased Risk

Abstract Background Sickle cell anemia (SCA) is the most common inherited hemoglobinopathy worldwide. Infection is a major cause of illness and death in children with SCA, especially in sub Saharan Africa where an estimated 50-90% of affected children die before their fifth birthday. Interventions to reduce the incidence and severity of infections are needed urgently. A high proportion of adults and children with SCA are zinc-deficient, and zinc deficiency leads to impaired immunity and an increased risk of infection. Zinc supplementation has been shown to decrease the risk of infection in adolescents and adults, but there is no data on the effectiveness of zinc for prevention of infection in children <5 years of age with SCA. Methods/Design The study will be a randomized, placebo-controlled, double-blind clinical trial in which 250 Ugandan children 1.00-4.99 years of age with SCA will receive daily zinc supplementation (10 mg oral dispersible tablet) or identical placebo for 12 months. Discussion If this trial shows a reduction in severe or invasive infection incidence, it would be the basis for a multi-site, multi-country clinical trial to assess real-world safety and efficacy of zinc in African children with SCA. Since zinc is safe, inexpensive, and easy to administer, this trial has the potential to improve the health of hundreds of thousands of African children with SCA through reduction of infection-related morbidity and mortality. Trial Registration Clinicaltrials.gov identifier: NCT03528434. Registered on May 17, 2018 Protocol Version: 1.0. Date: Dec 11, 2017 Sponsor: Indiana University. Sponsor’s protocol identifier: 1712339562

A Preliminary Report on Piracetam in Sickle Cell Anemia: A Double-Blind Crossover Clinical Trial and Effects on Erythrocyte Survival

1983 ◽  
Vol 3 (4) ◽  
pp. 233-235
Author(s):  
Muhammad A. Mikati ◽  
Hassan M. Solh ◽  
Denise E. Deryan ◽  
Itaf F. Sahli ◽  
Ibrahim A. Dabbous
Keyword(s):  
Clinical Trial ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Preliminary Report ◽  
Double Blind ◽  
Erythrocyte Survival

Impact of Hydroxyurea On Employment Among Patients with Sickle Cell Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2485-2485 ◽  
Author(s):  
Samir K. Ballas ◽  
Robert L Bauserman ◽  
William F. McCarthy ◽  
Myron A Waclawiw ◽  
Bruce A Barton
Keyword(s):  
Clinical Trial ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Conflicts Of Interest ◽  
Negative Impact ◽  
Double Blind Study ◽  
Full Time ◽  
Timely Initiation ◽  
Employment Patterns

Abstract Abstract 2485 Poster Board II-462 Introduction: Sickle cell disease (SCD) has a negative impact on education, career development, employment, and work history. Repeated painful crises and chronic complications (leg ulcers, retinopathy, etc.) can limit employment options and interfere with work attendance. Young adults frequently report that their health has interrupted educational plans and prevented their finding a full-time job. The purpose of this study is to examine employment patterns over time among SCD patients enrolled in the Multicenter Study of Hydroxyurea (MSH) in Sickle Cell Anemia, a randomized placebo-controlled double-blind study of whether hydroxyurea (HU) treatment could reduce the rate of painful crises in SCD. Patients and Methods: The N=299 adult patients in MSH were recruited from 21 sites across the U.S. and Canada, and were evenly distributed between males and females. Patients were at least 18 years old with a diagnosis of sickle cell anemia and at least 3 painful crises in the year prior to entry. The trial was terminated early due to a beneficial effect of HU on painful crises, but led to an observational follow-up and extension.Patients reported employment status at baseline and at 12, 24, and 36 months in the clinical trial; during the follow-up, employment data was collected in years 1-5 and 7-9. We categorized patients as ‘employed' (working full or part time) or ‘unemployed' (any other response, including unemployed, disabled, in school, retired, etc.). About 90% of all responses in this category were either unemployed or disabled, rather than other options such as in school.We examined employment history in 2 ways. First, changes from baseline to 24 months in the clinical trial (there was little data for 36 months due to the early termination) were categorized as continuous employment, continuous unemployment, shift from employment to unemployment, or from unemployment to employment; chi-square analyses were used to compare groups. Second, using all available data from the trial and follow-up, we calculated cumulative employment for each patient as the proportion of years employed out of all years of available data (up to the maximum possible of 12 years of data). This allowed us to obtain values for all patients despite missing data from some years. Linear regression models were used to compare groups.Employment history was compared between the placebo group and HU treatment responders and nonresponders (responders were defined as patients with % fetal hemoglobin < 15% before treatment and > 15% two years later). Many patients moved from placebo to HU following the clinical trial, but original group assignment was used for analyses because the HU group would have had the earliest and most consistent exposure to HU. Results: Descriptive data were suggestive of better employment outcomes for HU responders. During the clinical trial, 41% of responders and 29% of nonresponders were continuously employed or moved to employment. However, differences between responders, nonresponders and placebo patients were not statistically significant (p=.73). Across all years of data, responders were employed in 34% of years, versus about 30% for nonresponders and placebo patients. However, differences between groups were again not statistically significant (p=.71). Conclusions: Recurrent episodes of acute and chronic pain are characteristic of SCD. In MSH, HU treatment significantly reduced the rate of painful crises, the need for blood transfusion, and morbidity and mortality. Although some aspects of quality of life improved in this cohort of patients with moderate to severe SCD, employment patterns during the clinical trial and overall proportion of years in employment did not significantly differ. These findings point to two important aspects of HU treatment.First, employment effects may differ with more timely initiation of HU. MSH patients had moderate to severe SCD at enrollment, and some already had related disabilities (such as avascular necrosis) unaffected by HU. Earlier initiation of HU may prevent or delay onset of the most serious SCD complications that can negatively affect employment. Second, data such as those reported here may be of use in counseling young SCD patients regarding employment. The Americans with Disabilities Act defines rights of disabled/impaired persons in the workplace and awareness of this may lessen stress due to fear of losing a job or being unable to find employment. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document