Purified Poloxamer 188 for Treatment of Acute Vaso-occlusive Crisis of Sickle Cell Disease

Orringer, Eugene P.; Casella, James F.; Ataga, Kenneth I.; Koshy, Mabel; Adams-Graves, Patricia; Luchtman‐Jones, Lori; Wun, Theodore; Watanabe, Masayo; Shafer, Frank; Kutlar, Abdullah; Abboud, Miguel R.; Steinberg, Martin H.; Adler, Brian K.; Swerdlow, Paul; Terregino, Carol A.; Saccente, Suzanne; Files, Beatrice; Ballas, Samir K.; Brown, Robert C.; Wojtowicz‐Praga, Slawomir; Grindel, J M

doi:10.1001/jama.286.17.2099

Cited by 183 publications

(138 citation statements)

References 31 publications

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“…[5][6][7][8] Recent studies of novel agents for VOC treatment, including inhaled nitric oxide and purified poloxamer-188, demonstrated little or no clinical benefit. 9,10 Although some centers in larger cities have established "day hospitals" for the specialized care of SCD patients with VOC, 11 the vast majority of initial medical care occurs in hospital emergency departments (EDs). In both the ED and the inpatient setting, both patients and parents report a high level of dissatisfaction with VOC treatment, including delays in receiving treatment and undertreatment of pain.…”

Section: What This Study Addsmentioning

confidence: 99%

Timing of Opioid Administration as a Quality Indicator for Pain Crises in Sickle Cell Disease

Mathias¹,

McCavit²

2015

PEDIATRICS

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Section: What This Study Addsmentioning

confidence: 99%

Timing of Opioid Administration as a Quality Indicator for Pain Crises in Sickle Cell Disease

Mathias¹,

McCavit²

2015

PEDIATRICS

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“…83 However, a subsequent larger randomized, placebo-controlled Phase III trial showed a statistically significant but clinically disappointing small (9-hour) decrease in the duration of painful episodes compared with the patients receiving placebo. 84 In subgroup analysis, children and patients who were receiving concomitant HU had a more significant reduction in crisis duration (16-21 hours). Whether these findings represented more efficacy of this agent in these subgroups, or a more effective statistical analysis strategy, was uncertain.…”

Section: "Painful Lessons" -Past Treatment Failuresmentioning

confidence: 98%

Orphan drugs for sickle vaso-occlusion: dawn of a new era of targeted treatment

Dampier¹

2015

ODRR

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Abstract:While an orphan disease in the USA, sickle cell disease (SCD), a group of genetic disorders of hemoglobin structure and function, is a major public health problem in much of the rest of the world, particularly sub-Saharan Africa. The pathophysiology of SCD stems from the formation of sickle hemoglobin polymers that deform the erythrocyte into a characteristic sickle shape, the rapidity of which is regulated by its intracellular hemoglobin concentration. Subsequent vaso-occlusion is dependent on adhesion of sickled erythrocytes, and perhaps other cellular elements, including leucocytes and platelets, to abnormal vascular endothelium using a number of receptor-ligand pairs. This propensity for vaso-occlusion may be enhanced by altered vascular tone from excessive amounts of vaso-constrictive factors or diminished amounts of vasodilatory factors. Acute pain is the hallmark symptom caused by sickle polymer formation and subsequent vaso-occlusion, and is represented in the endpoints of most previous and current clinical trial designs. Numerous failures of prior investigational agents have frustrated clinicians and patients alike. Hydroxyurea is currently the only US Food and Drug Administration-approved drug for SCD and reduces the frequency of vaso-occlusive complications in many individuals. A considerable therapeutic need remains as hydroxyurea usage is currently not approved for all types of SCD, is not always clinically effective, and requires frequent monitoring. Recent improvements in our understanding of SCD pathophysiology have generated many new therapeutic targets and associated investigational agents. For example, a number of more specific fetal hemoglobin inducers and several therapies to reduce sickle polymer formation are being tested in preclinical and early phase clinical trials. Several agents that target receptor-ligand interactions which mediate cellular adhesion to vascular endothelium have shown considerable promise and are entering Phase III trials, but present some continuing challenges in clinical trial design and conduct. Gene therapy trials are poised to start and offer the potential for curative therapy.

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“…11 In a RCT enrolling children and adults, purified poloxamer 188, a non-FDA approved surfactant, showed a small overall effect in reducing the duration of a painful episode. 12 A dedicated day hospital has been shown to be effective in reducing hospital admissions and length of stay for painful episodes.…”

Section: Treatment Of Acute Painful Episodesmentioning

confidence: 99%

An Evidence-Based Approach to the Treatment of Adults with Sickle Cell Disease

Lottenberg

Hassell²

2005

Hematology

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The application of evidence-based medicine to the management of adults with sickle cell disease (SCD) is currently primarily driven by clinical expertise and patient preference, as there is a paucity of randomized controlled trial (RCT) data to guide decision-making. A summary of SCD management principles in the areas of health care maintenance, transfusion therapy, treatment and prevention of painful episodes, acute chest syndrome, stroke, renal disease, contraception and pregnancy, and priapism is predominantly based on the authors' interpretation of available observational studies as well as the opinions of experts in SCD. RCTs impacting current practices address use of hydroxyurea to prevent painful episodes and acute chest syndrome, intensity of pre-operative transfusion, transfusion during pregnancy, and angiotensinconverting enzyme inhibitor therapy for proteinuria, but most issues in adult SCD care have not been rigorously studied and management may not be appropriately extrapolated from pediatric data. While challenging clinical problems need to be addressed by RCTs, there is also the need for development of practice guidelines using formal methodological strategies. This brief review is not a substitute for the process but provides a literature-based approach to making treatment decisions when caring for adults with SCD.

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Purified Poloxamer 188 for Treatment of Acute Vaso-occlusive Crisis of Sickle Cell Disease

Cited by 183 publications

References 31 publications

Timing of Opioid Administration as a Quality Indicator for Pain Crises in Sickle Cell Disease

Timing of Opioid Administration as a Quality Indicator for Pain Crises in Sickle Cell Disease

Orphan drugs for sickle vaso-occlusion: dawn of a new era of targeted treatment

An Evidence-Based Approach to the Treatment of Adults with Sickle Cell Disease

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