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2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Andy Bauleni ◽  
Fentanesh N. Tiruneh ◽  
Tisungane E. Mwenyenkulu ◽  
Owen Nkoka ◽  
Gowokani C. Chirwa ◽  
...  

Abstract Background Despite the limited knowledge regarding the effects of deworming medication (DM) on nutritional indicators in sub-Saharan Africa (SSA), deworming programmes continue to be implemented in resource-limited countries. Therefore, the current study aimed to examine the effects of DM on anaemia among children aged 6–59 months in SSA. Methods The analysis was performed using data obtained from 17 demographic and health surveys (DHSs) conducted in SSA. Children were considered to be anaemic if their haemoglobin (Hb) concentration was less than 11.0 g/dl, adjusting for altitude. To account for both multiple measures at the cluster level and the clustering of children within the same country, generalized linear mixed models were used to analyse the anaemia outcomes in 50,075 children aged 6–59 months. Results Overall, anaemia was reported in 61.8% of the children, and their median Hb concentration was 10.5 g/dl (interquartile range 9.4–11.5). The prevalence of anaemia ranged from 34.5% in Rwanda to 81.1% in Mali. Multivariate analyses showed that children who did not receive DM had increased odds of being anaemic (adjusted odds ratio [aOR]: 1.11; 95% confidence interval [CI] 1.07–1.16). Conclusions The current study revealed that DM can decrease the risk of anaemia among preschool-age children (pre-SAC) in SSA. Thus, tailored public health programmes aimed at reducing childhood anaemia need to consider deworming. However, longitudinal studies are needed to validate the association that has been reported in this cross-sectional study. Graphical Abstract


2022 ◽  
Vol 8 ◽  
Author(s):  
Yu-Mei Liu ◽  
Hui Huang ◽  
Jie Gao ◽  
Jian Zhou ◽  
Hai-Chen Chu

This study aimed to determine the relationship between hemoglobin (Hb) concentration and post-operative delirium (POD) in elderly patients undergoing femoral neck fracture (FNF) surgery and to investigate whether the change in Hb concentration is associated with POD and the risk factors for POD. A total of 889 patients admitted with FNF between January 2016 and December 2020 were enrolled in this single-center, retrospective, case–control study. Hb concentrations were determined at admission and post-operative day 1 and the change in Hb concentration was defined as the absolute value of difference in pre-operative and post-operative Hb concentration. POD was assessed using the Confusion Assessment Method for the Intensive Care Unit (ICU) or the Confusion Assessment Method once a daily after surgery. The logistic regression analysis was performed for statistical analysis. In total, 172 (19.3%) patients developed POD and 151 (87.8%) patients developed POD within post-operative 3 days. Low pre-operative Hb concentration [p = 0.026, odds ratio (OR) = 0.978] and significant change in Hb concentration (p = 0.006, OR = 1.033) were significantly associated with POD. After excluding change in Hb concentration or pre-operative Hb concentration, neither of them was significantly associated with POD (p > 0.05). The interaction analysis of change in Hb concentration and pre-operative Hb concentration in the logistic regression model was negative. There was no significant relationship between post-operative Hb concentration and POD. Age (p < 0.001, OR = 1.072), stroke history (p = 0.003, OR = 2.489), post-operative ICU transfer (p = 0.007, OR = 1.981), and visual analog scale score within post-operative 2 days (p1 = 0.016 and p2 = 0.006) were independently associated with POD in the logistic regression analysis. Patients with low pre-operative Hb concentrations and high changes in Hb concentration seem to have an increased risk of POD and should receive more attention. Old age, stroke history, post-operative ICU transfer, and pain within post-operative 2 days were significantly associated with POD.


Author(s):  
Muhammad Y ◽  
◽  
Jatau ID ◽  

In this study, biochemical and haematological effects of kaempferol in stress induced by experimental Eimeria tenella infection in two weeks old broiler chickens was investigated. Sixty-day old broilers were randomly allotted into six groups (I-VI) of ten broilers each and brooded for two weeks with commercial broiler feed (vital feed®) and provided water ad libitum. At two weeks of age broilers in group I served as non-infected control. Broilers in groups II- VI were infected with Eimeria tenella sporulated oocyst (104/ml) via oral inoculation. After infection was established, broilers in groups II-IV were treated per os with 1 mg/kg, 1.5 mg/kg and 2 mg/kg of kaempferol respectively. Broilers in group V were treated for five days with amprolium, 1.25 g/L in drinking water. Broilers in group VI served as infected untreated control. Five days post infection; all broilers were sacrificed by severing their jugular veins. Blood sample was collected from each broiler in a plane sample container devoid of anticoagulant so as to harvest serum for serology while Ethylenediamine tetra-acetic acid (EDTA) bottles were used to collect 1 ml of blood from each bird for haematology. Concentrations of antioxidant (GPx, CAT and SOD) and liver enzymes (ALT, AST and ALP) were determined. Data obtained was analyzed using pad prism version 5.0. There were statistically significant (P<0.05) reductions in the mean values of liver enzymes (ALT, AST, ALP) in groups II, III and IV in a dose dependent manner when compared to group VI. Similarly, the mean values of antioxidant (GPx, CAT and SOD) enzymes increased significantly significant (P<0.05) in groups II, III and IV in a dose dependent manner when compared to group VI. No significant (P>0.05) difference in the mean values of antioxidants and liver enzymes were recorded between groups II, III and IV and when compared to group V. Mean Packed Cell Volume (PCV), haemoglobin (Hb) concentration and Red Blood Cell (RBC) count significantly (P<0.05) increased in groups II, III, and IV in a dose dependent manner. Similarly, PCV, Hb concentration and RBC count were significantly (P<0.05) increased in groups II, III, and IV when compared with VI. No significant (P>0.05) difference in the mean values of PCV, Hb and RBC were recorded in groups treated with kaempferol and group treated with amprolium. It was observed in this study that kaempferol improved the serum level of antioxidants and liver enzymes as well as and haematological parameters and also reduced the level of pathology in the caecum of broilers infected with Eimeria tenella in this study.


Author(s):  
Mayada M. Moustafa ◽  
Ali Abdulhussain Kasim ◽  
Rawaa Dawood Al-Janabi

Hemogloin (Hb) and serum ferritin levels are used to assess anemia in pregnancy. Some studies referred to the influence of maternal age, body mass index (BMI) and parity on Hb and serum ferritin levels. The study aimed to examine the possible association of maternal Hb and serum ferritin with maternal age, parity, and BMI in a sample of pregnant women in Baghdad.  Ninety healthy pregnant women, grouped in three equal groups according to the pregnancy trimester, and thirty apparently healthy non-pregnant women from Baghdad were enrolled in this observational study.  Blood and serum samples were obtained for the estimation of Hb and serum ferritin levels. The pooled data of participants showed a negative correlation between parity and each of blood Hb concentrations (r= -0.147, P=0.046) and plasma ferritin levels (r= -0.186, P= 0.038). The negative correlation of parity with blood Hb concentration was reported in participants in the third trimester of pregnancy (r= -0.270, P=0.048); and between parity and plasma ferritin levels in the second (r= -0.088, P= 0.046) and third (r= -0.398, P=0.029) trimester pregnant. The study did not report a significant correlation between age and BMI with blood Hb concentrations or serum ferritin levels in pregnant women at any trimester of pregnancy. There is a negative correlation between parity and each of blood Hb concentration and serum ferritin levels in pregnant women in Baghdad. While, there is no such correlation with maternal age and BMI at any trimester of pregnancy.


2021 ◽  
Vol 9 ◽  
Author(s):  
Jiaojiao Ren ◽  
Zhenghe Wang ◽  
Yujie Zhang ◽  
Peidong Zhang ◽  
Jianmeng Zhou ◽  
...  

Introduction: The association patterns of hemoglobin (HB) concentrations with mortality among the longevity older adults are unclear. We aimed to evaluate the relationship among older adults form Chinese longevity regions.Methods: We included 1,785 older adults aged ≥65 years (mean age, 86.7 years; 1,002 women, 783 men) from the community-based Chinese Longitudinal Healthy Longevity Survey. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality using multivariable Cox proportional hazards models and Cox models with restricted cubic spline.Results: In total, 999 deaths occurred during a median follow-up of 5.4 years from 2011 to 2017. Restricted cubic spline analysis found no non-linear association between HB concentrations and all-cause mortality after a full adjustment for covariates among the older adults form longevity regions (p &gt; 0.05 for non-linearity). The risk for all-cause mortality was significantly higher in the groups with HB concentration of &lt;11.0 g/dL (HR: 1.37, 95% CI: 1.10–1.70) and 11.0–12.0 g/dL (HR: 1.25, 95% CI: 1.01–1.54); the risk of all-cause mortality was significantly lower in the groups with HB concentration ≥14.0 g/dL (HR: 0.76, 95% CI: 0.60–0.97) compared with the reference group (13.0–13.9 g/dL).Conclusions: Among older adults form Chinese longevity regions, HB concentrations were found to be inversely and linearly associated with all-cause mortality. Further prospective intervention trials are needed to confirm whether higher HB concentrations had a lower risk of mortality in these older adults.


2021 ◽  
Vol 10 (22) ◽  
pp. 5411
Author(s):  
Miguel A. Santos-Silva ◽  
Nuno Sousa ◽  
João Carlos Sousa

Anemia and inflammation are common clinical conditions in emergency departments. This study explored a cohort of patients admitted to the emergency department with a particular interest in determining the frequency of anemia and inflammation and the association between hemoglobin (Hb) and C-reactive protein (CRP) concentrations. The study included 125 patients categorized according to their demographic (gender and age) and clinical condition (Hb and CRP concentrations, pathological background, and diagnostic). We found that anemia and inflammation were simultaneously present in 36.0% of the cohort, reaching 67.0% in patients that were subsequently hospitalized. The Hb level was significantly lower in patients with elevated concentration of CRP when compared to individuals with normal CRP levels (11.58 ± 2.23 vs. 13.25 ± 1.80, p = 0.001); furthermore, we found a significantly negative correlation between Hb concentration and the CRP level (rs = −0.42, p < 0.001). The linear regression model applied to the cohort showed that CRP levels explain 15% of Hb variations. The sensitivity of the CRP/Hb ratio (cut-off = 1.32) as a predictor of hospitalization was 80.0%, with a specificity of 68.4% for all patients. These findings confirmed the prevalence of anemia and inflammation and identified a moderate but significant association between Hb and serum CRP in a heterogeneous group of patients admitted to the emergency department.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jiang-Ming Chen ◽  
Wei-Jian Zhu ◽  
Jie Liu ◽  
Gui-Zhen Wang ◽  
Xiao-Qin Chen ◽  
...  

AbstractThalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5038-5038
Author(s):  
Claudio Cerchione ◽  
Fiorella Alfinito ◽  
Orsola Vitagliano ◽  
Ilaria Soriente ◽  
Paolo Danise ◽  
...  

Abstract Erythropoiesis stimulating agents (ESAs) are the frontline treatment in low-risk anemic MDS patients and an employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. It's matter of debate whether the clinical response is a result of proliferation and maturation of the dysplastic clone or stimulation of residual normal erythropoiesis by ESAs. Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS: an analysis of the erythropoietic response to ESAs therapy in a cohort of anemic non trasfusion-dependent MDS patients, enrolled in a retrospective register, RECAMDS, subgroup of Italian register, was performed. 183 patients, treated with standard-dose ESAs, have been retrospectively analyzed. Data analysis was performed, according to IWG 2006 criteria, at the baseline, after 3 and 6 months of continuous treatment, with a subanalysis of the patients according to WHO and R-IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl, mean serum EPO concentration: 51 mU/L, after a mean time from diagnosis of 6 months (r.1-118). ORR was 83.6% (153/183), no difference among WHO and IPSS subgroups was found: 132/183 (72.1%) achieved response after 3 months of treatment, while other 21/183 (11.2%) after 6 months. 19 patients with stable disease (non-responders, according to IWG criteria), in which treatment was continued, achieved response after 9 months. In the macrocytic-responders group 83.2% exhibits again macrocytosis after 3 months, while 16.8% become normocytic. In the normocytic-responders group 89.8% exhibits again normocytosis, while 10.2% become macrocytic: in these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia, with transfusion-dependence, regarded as first signs of progression of disease. Non-responders were 30/183 (16.3%): in the macrocytic non-responders group 89% exhibit again macrocytosis after 3 months, while 11% become normocytic; in the normocytic group 76% exhibits again macrocytosis, while 24% become normocytic. These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs mainly stimulating erythroid production in MDS clones; in the minority of patients probably it happens recruiting residual polyclonal erythropoiesis. It is interesting to note that stimulating effects of ESAs last even when the expression of dysplasia progresses. Figure 1 Figure 1. Disclosures Martinelli: Roche: Consultancy; Stemline Therapeutics: Consultancy; Abbvie: Consultancy; Jazz Pharmaceuticals: Consultancy; Celgene /BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Incyte: Consultancy; Daichii Sankyo: Consultancy; Astellas: Consultancy, Speakers Bureau.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 576-576
Author(s):  
Kevin H.M. Kuo ◽  
D. Mark Layton ◽  
Ashutosh Lal ◽  
Hanny Al-Samkari ◽  
Joy Bhatia ◽  
...  

Abstract Background: The thalassemias are a group of red blood cell (RBC) disorders in which ineffective erythropoiesis and hemolysis occur due to imbalanced production and precipitation of globin chains. Thalassemic RBCs have insufficient levels of ATP to meet increased energy demands associated with globin chain imbalance, protein degradation, and cellular oxidative stress responses. Mitapivat (AG-348) is a first-in-class, small-molecule, oral activator of RBC pyruvate kinase (PKR), a key enzyme regulating ATP production via glycolysis. In a phase 2, open-label trial of mitapivat in adults with α- or β-non-transfusion-dependent (NTD) thalassemia (NCT03692052), 80.0% (16/20) of patients (pts) met the primary endpoint of a hemoglobin (Hb) response (increase ≥ 1.0 g/dL from baseline at 1 or more assessments between Wks 4-12, inclusive). Improvements in markers of hemolysis and erythropoiesis were also observed in pts and mitapivat was generally well tolerated. Methods: Pts aged ≥ 18 (yrs) with a known medical history of α- or β-thalassemia, Hb concentration of ≤ 10.0 g/dL, and ≤ 5 RBC units transfused in prior 24 wks and none in 8 wks prior to study drug were eligible for the study. All pts started mitapivat at 50 mg twice daily (BID), escalating to 100 mg BID based on individual safety and Hb assessments. After completion of the 24-wk core period, pts were continued on mitapivat treatment in the extension period if they had achieved a Hb response, or a delayed Hb response (Hb increase of ≥ 1.0 g/dL at ≥ 1 assessment after Wk 12), with no ongoing grade ≥ 3 treatment-emergent adverse events (AE) related to study drug. Eligible pts continued mitapivat at the dose received at their Wk 24 visit. Study visits are conducted every 12 wks and will continue for up to 10 yrs. The extension period of the study is ongoing, here we report data up to Wk 72 visit (data cutoff March 27, 2021). Results: Of the 19 pts who completed the core period, 17 entered the extension period. During the extension period, 16 pts received 100 mg BID mitapivat and 1 received 50 mg BID. As of the cutoff date, 1 pt had discontinued (patient decision). Median (range, in wks) duration of mitapivat treatment for pts who entered the extension period was 70.9; (54.7, 105.6), with 8 of 17 pts receiving 72 wks or more of treatment as of the cutoff date for this analysis. The Median age of pts who entered the extension period was 44 yrs (range 29, 67). Mean baseline (standard deviation [SD]) Hb, total bilirubin and lactate dehydrogenase (LDH) was 8.1 (1.2) g/dL, 40.1 (26.2) μmol/L and 272.4 (121.7) U/L, respectively. Median baseline erythropoietin (EPO) was 70.5 (range 15, 11191) IU/L. Improvements in Hb concentration achieved in the core period were sustained in the extension study (n = 8 at Wk 72; Figure 1). Mean Hb (SD) increase from baseline to Wk 60 (which includes 4 pts with α- and 9 with β-thalassemia) and Wk 72 (which includes 8 pts with β-thalassemia) were 1.5 (0.4) g/dL and 1.7 (0.5) g/dL, respectively. Improvements in markers of hemolysis and ineffective erythropoiesis observed in the core period were maintained in the extension period up to Wk 72 (mean [SD] bilirubin and LDH, -15.8 [16.6] μmol/L and -63.6 [216.0] U/L, respectively; median [range] EPO, -33.0 [-72.0, -16.0] IU/L). The safety profile was consistent with that observed during the core period. AEs occurring in ≥ 15% of pts during the extension period were headache (5/17) and back pain (3/17), none of which were grade ≥ 3. No notable trends for changes in bone mineral density were observed (Figure 2). There were no treatment-related serious AEs during the extension period. Conclusions: In pts with either α- or β-thalassemia, a favorable efficacy-safety profile was observed with long-term treatment with mitapivat. Results show sustained improvements in Hb, hemolysis and ineffective erythropoiesis - despite the globin genotypic heterogeneity of the cohort - and no new safety findings. Mitapivat, through its unique mechanism of action, may represent a novel therapeutic approach for this condition. Two phase 3 trials of mitapivat in α- and β-thalassemia, one in pts who are NTD and one in pts who are transfusion-dependent, will be initiated in 2021. Figure 1 Figure 1. Disclosures Kuo: Bluebird Bio: Consultancy; Alexion: Consultancy, Honoraria; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; Apellis: Consultancy; Pfizer: Consultancy, Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy. Layton: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cerus: Membership on an entity's Board of Directors or advisory committees. Lal: Chiesi: Consultancy; Agios Pharmaceuticals: Consultancy; bluebird bio, Inc.: Research Funding; La Jolla Pharmaceutical Company: Research Funding; Terumo Corporations: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Insight Magnetics: Research Funding; Protagonist Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding. Al-Samkari: Dova/Sobi: Consultancy, Research Funding; Moderna: Consultancy; Argenx: Consultancy; Rigel: Consultancy; Amgen: Research Funding; Novartis: Consultancy; Agios: Consultancy, Research Funding. Bhatia: Agios Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Kosinski: Agios Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Tong: Agios Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Lynch: Agios Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Uhlig: Agios Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Vichinsky: Agios Pharmaceuticals: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3109-3109
Author(s):  
Joanna Howard ◽  
Kevin H.M. Kuo ◽  
Abdulafeez Oluyadi ◽  
Hui Shao ◽  
Susan Morris ◽  
...  

Abstract Background: Sickle cell disease (SCD) is a life-threatening, hereditary hemoglobin (Hb) disorder characterized by chronic hemolytic anemia, pain, end-organ damage, and poor quality of life. The key pathology is red blood cell (RBC) sickling due to polymerization of deoxygenated sickle Hb (HbS), which can be exacerbated by increased levels of the glycolytic metabolite 2,3-diphosphoglycerate (2,3-DPG), and decreased ATP. Sickled RBCs are rigid, not deformable, and fragile, resulting in vaso-occlusion triggering pain and chronic hemolysis. SCD treatment options are limited, with an unmet need for safe and effective therapies to improve anemia and reduce pain. Mitapivat is an investigational, first-in-class, oral, small-molecule allosteric activator of the RBC-specific form of pyruvate kinase (PKR), a key enzyme in glycolysis. Activation of wild-type PKR decreases 2,3-DPG and increases ATP, which may reduce HbS polymerization, RBC sickling, and hemolysis in SCD. Data from the Phase 1 National Institutes of Health multiple ascending dose study of up to 100 mg mitapivat twice daily (BID) in SCD (NCT04000165) showed that mitapivat was safe and tolerable, and was associated with a dose-dependent increase in ATP and decrease in 2,3-DPG, in addition to improvements in anemia and hemolytic markers. Based on these results, a Phase 2/3 study investigating the safety and efficacy of mitapivat in patients (pts) with SCD is planned. Methods: This Phase 2/3, double-blind, randomized, placebo-controlled, multicenter study aims to evaluate the efficacy and safety of mitapivat in pts with SCD. Eligible: pts ≥ 16 years of age with documented SCD (HbSS, HbSC, HbSβ 0/HbSβ + thalassemia, other SCD variants), 2-10 sickle cell pain crises (SCPCs; acute pain needing medical contact, acute chest syndrome, priapism, hepatic or splenic sequestration) in the prior 12 months, and an Hb level of 5.5-10.5 g/dL. If taking hydroxyurea (HU), the dose must be stable for ≥ 90 days before starting study drug. Not eligible: pts receiving regularly scheduled blood transfusions, with severe kidney disease or hepatobiliary disorders, currently receiving treatment with SCD therapies (excluding HU) or who have received gene therapy, bone marrow or stem cell transplantation. In the double-blind Phase 2 part of the study, 69 pts will be randomized (1:1:1) to receive 50 mg mitapivat, 100 mg mitapivat, or placebo BID for 12 weeks. The primary objective of the Phase 2 part of the study is to determine the recommended Phase 3 dose of mitapivat by evaluating anemia and safety vs placebo via the following endpoints: Hb response, defined as a ≥ 1.0 g/dL increase in average Hb concentration over Weeks 10-12 compared with baseline; and type, severity, and relationship of adverse events (AEs) and serious AEs (SAEs). In the double-blind Phase 3 part of the study, 198 pts who did not participate in the Phase 2 study will be randomized (2:1) to receive the selected Phase 3 dose of mitapivat or placebo, BID, for 52 weeks, stratified by the number of SCPCs in the prior year (&lt; 5, ≥ 5) and by HU use. The primary objectives of the Phase 3 study are to determine the effect of mitapivat vs placebo on anemia in pts with SCD, measured by Hb response, defined as a ≥ 1.0 g/dL increase in average Hb concentration over Weeks 24-52 compared with baseline, and to determine the effect of mitapivat vs placebo on SCPC, measured by annualized rate of SCPCs. Key secondary endpoints include change over Weeks 24-52 compared with baseline in the following: average Hb concentration, indirect bilirubin, percent reticulocyte, and Patient-Reported Outcomes Measurement Information System ® (PROMIS) fatigue 13a Short Form scores; annualized frequency of hospitalizations for SCPC. Other secondary objectives include evaluation of effect on additional markers of hemolysis and erythropoiesis, additional clinical efficacy measures related to SCPC, additional patient-reported measures of fatigue and pain, physical activity, safety, and pharmacokinetics/pharmacodynamics of mitapivat. Pts who complete the double-blind period of either the Phase 2 or Phase 3 part of the study will be eligible to receive mitapivat for an additional 216 weeks in the open-label extension period. Results: Not yet available Conclusion: This Phase 2/3 study will investigate the efficacy and safety of the pyruvate kinase activator mitapivat in pts ≥ 16 years of age with SCD and enrollment will begin in 2021. Figure 1 Figure 1. Disclosures Howard: Resonance Health: Honoraria; Novartis: Consultancy, Honoraria; Bluebird Bio: Research Funding; Forma Therapeutics: Consultancy; Agios Pharmaceuticals: Consultancy; Novo Nordisk: Consultancy; Global Blood Therapeutics: Consultancy; Imara: Consultancy, Honoraria. Kuo: Bluebird Bio: Consultancy; Apellis: Consultancy; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Pfizer: Consultancy, Research Funding; Alexion: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bioverativ: Membership on an entity's Board of Directors or advisory committees. Oluyadi: Agios Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Shao: Agios Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Morris: Agios Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Zaidi: Agios Pharmaceuticals: Current Employment. Van Beers: RR Mechatronics: Research Funding; Novartis: Research Funding; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding.


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