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Intraoperative use of tranexamic acid to reduce blood loss during cytoreductive surgery for advanced ovarian cancer: A randomized controlled clinical trial
Yang X, Chai M, Xia L, He Z, Wu X, Zhang J
Acta obstetricia et gynecologica Scandinavica. 2023
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Abstract
INTRODUCTION Tranexamic acid reduces blood loss and allogeneic transfusion requirements in various surgical procedures. The role of tranexamic acid during cytoreductive procedures in advanced ovarian cancer is not clear. MATERIAL AND METHODS This was a single center randomized, controlled, three-armed clinical trial. A total of 150 ovarian cancer patients undergoing cytoreductive surgery were recruited and assigned to three groups (n = 50/group): the control group (normal saline), low-dose group (10 mg/kg bolus + 1 mg/kg continuous infusion of tranexamic acid), and high-dose group (20 mg/kg bolus + 5 mg/kg continuous infusion of tranexamic acid). The primary endpoint was intraoperative blood loss volume and total blood loss volume, and secondary endpoints included intraoperative blood transfusion volumes, vasoactive agent consumption, admission into the intensive care unit, and incidence of postoperative complications within postoperative 30 days. The study was registered at ClinicalTrials.gov ID: NCT04360629. RESULTS The patients in the high-dose group had less intraoperative (median [IQR]: 625.3 mL [343.5-1210.5]) and total blood loss volume (748.9 mL [292.2-1650.2]) than those in the control group (1015.5 mL [679.4-1015.5], p = 0.012; and 1700.7 mL [458.7-2419.8], p = 0.004, respectively). In contrast, the intraoperative (992.5 mL [539.0-1404.0], p = 0.874) and total blood loss volume (1025.0 mL [381.8-1819.9], p = 0.113) was not significantly reduced in the low-dose group when compared with the control group. Correspondingly, the relative risk of blood transfusion (RR [95% CI], 0.405 [0.180-0.909], p = 0.028) was reduced in the high-dose group and required less intraoperative noradrenaline (881.0 ± 438.3 mg) to maintain stable hemodynamics than the control group (1548.0 ± 349.8 mg, p = 0.001). Furthermore, compared with the control group, the two tranexamic acid groups had decreased intensive care unit admission rates (p = 0.016) without increasing the incidence of postoperative seizure, acute kidney injury, and thromboembolism. CONCLUSIONS High-dose tranexamic acid is more effective in reducing blood loss and blood transfusion without increasing the risk of postoperative complications. The high-dose regime tended to have a better risk-benefit profile.
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Individualized red-cell transfusion strategy for non-cardiac surgery in adults: a randomized controlled trial
Liao R, Liu J, Zhang W, Zheng H, Zhu Z, Sun H, Yu Z, Jia H, Sun Y, Qin L, et al
Chinese medical journal. 2023
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Abstract
BACKGROUND Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion. METHODS Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test). RESULTS We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P<0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P<0.001). No statistical differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies. CONCLUSION The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries. TRIAL REGISTRATION ClinicalTrials.gov, NCT01597232.
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[A multicenter, double-blind, randomized controlled clinical trial comparing ergometrine with oxytocin and oxytocin alone for prevention of postpartum hemorrhage at cesarean section]
He GL, Pan TY, Liu XX, He SY, Zhang L, Feng WS, Zhang J, He J, Xin W, Zhou YL, et al
Zhonghua fu chan ke za zhi. 2022;57(11):836-842
Abstract
Objective: To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS). Methods: This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration. Results: (1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant (P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups (P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant (P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion: The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.
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A randomized controlled trial to compare the efficacy of regenerated and non-regenerated oxidized cellulose gauze for the secondary treatment of local bleeding in patients undergoing hepatic resection
Zhang C, Fu D, Wang F, Zhong X, Yang L, Wu G, Li B, Zhang J
Annals of surgical treatment and research. 2021;100(4):193-199
Abstract
PURPOSE Oxidized cellulose is available in many forms, but manufactured using either a regenerated or non-regenerated process. In this study, we evaluated the effects of 2 different hemostatic agents for the treatment of local bleeding in patients undergoing hepatic resection. METHODS This was a monocentric, parallel-group, randomized, and controlled clinical trial to compare oxidized regenerated cellulose gauze (ORCG) with oxidized non-regenerated cellulose gauze (ONRCG) in patients undergoing hepatectomy. The primary endpoint was the time to hemostasis at the target bleeding site. The secondary endpoints were the postoperative drainage volume on the first 2 days after surgery and the hospital stay. RESULTS There was no significant difference between the ORCG and ONRCG groups in time to hemostasis from column analysis (238.8 ± 121.6 seconds vs. 193.7 ± 85.3 seconds, P = 0.068), and there were no differences in the rates of hemostatic success between the 2 groups at 120 seconds (18.4% vs. 24.3%; odds ratio [OR], 0.703; 95% confidence interval [CI], 0.231-2.136) and 300 seconds (71.1% vs. 89.2%; OR, 0.298; 95% CI, 0.085-1.041). However, the ONRCG group was superior to the ORCG group in hemostasis according to the survival analysis (log-rank test, P = 0.044). Moreover, there were also no significant differences between the 2 groups in postoperative drainage volume on the first 2 days (P = 0.436, P = 0.381) and hospital stay (P = 0.537, P = 0.200). CONCLUSION ONRCG was not inferior to ORCG as a hemostatic agent in patients undergoing liver resection.
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EXPRESS: Safety and Efficacy of Remote Ischemic Conditioning for the Treatment of Intracerebral Hemorrhage: A Proof-of-Concept Randomized Controlled Trial
Zhao W, Jiang F, Li S, Liu G, Wu C, Wang Y, Ren C, Zhang J, Gu F, Zhang Q, et al
International journal of stroke : official journal of the International Stroke Society. 2021;:17474930211006580
Abstract
Background Remote ischemic conditioning (RIC) can promote hematoma resolution, attenuate brain edema, and improve neurological recovery in animal models of intracerebral hemorrhage (ICH). Aims This study aimed to evaluate the safety and preliminary efficacy of RIC in patients with ICH.Methods In this multicenter, randomized, controlled trial, 40 subjects with supratentorial ICH presenting within 24-48 hours of onset were randomly assigned to receive medical therapy plus RIC for consecutive 7 days or medical therapy alone. The primary safety outcome was neurological deterioration within 7 days of enrollment, and the primary efficacy outcome was the changes of hematoma volume on CT images. Other outcomes included hematoma resolution rate at 7 d ([hematoma volume at 7 d â hematoma volume at baseline]/hematoma volume at baseline), perihematomal edema (PHE), and functional outcome at 90 days. Results The mean age was 59.3±11.7 years and hematoma volume was 13.9±4.5 mL. No subjects experienced neurological deterioration within 7 days of enrollment, and no subject died or experienced RIC-associated adverse events during the study period. At baseline, the hematoma volumes were 14.19±5.07 mL in the control group and 13.55±3.99 mL in the RIC group, and they were 8.54±3.99 mL and 6.95±2.71 mL at 7 days after enrollment, respectively, not a significant difference (p>0.05 each). The hematoma resolution rate in the RIC group (49.25±9.17%) was significantly higher than in the control group (41.92±9.14%; MD, 7.3%; 95% CI, 1.51% to 13.16%; p=0.015). The absolute PHE volume was 17.27±8.34 mL in the control group and 12.92±7.30 mL in the RIC group at 7 days after enrollment, not a significant between-group difference (p=0.087), but the relative PHE in the RIC group (1.77±0.39) was significantly lower than in the control group (2.02±0.27; MD, 0.25; 95% CI, 0.39-0.47; p=0.023). At 90-day follow-up, 13 subjects (65%) in the RIC group and 12 subjects (60%) in the control group achieved favorable functional outcomes (mRS scoreâ¤3), not a significant between-group difference (p=0.744).Conclusions Repeated daily RIC for consecutive 7 days was safe and well-tolerated in patients with ICH, and it may be able to improve hematoma resolution rate and reduce relative PHE. However, effects RIC on the absolute hematoma and PHE volume and functional outcomes in this patient population need further investigations.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03930940.
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Effect of Multiple Doses of Intravenous Tranexamic Acid on Perioperative Blood Loss in Total Knee Arthroplasty: A Randomized Controlled Study
Kang BX, Li YL, Xu H, Gao CX, Zhong S, Zhang J, Xie J, Sun ST, Xu XR, Zhao C, et al
Orthopaedic surgery. 2021;13(1):126-133
Abstract
OBJECTIVE To identify the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) following primary total knee arthroplasty (TKA) with a tourniquet. METHODS This is a single-blind randomized controlled study that recruited osteoarthritis patients who had undergone primary unilateral TKA from May 2019 to May 2020 at our medical center. A total of 300 patients were randomly divided into three groups to receive: one dose (1 g) of IV-TXA before skin incision combined with one dose (1.5 g) of intra-articular tranexamic acid(IA-TXA) followed by a single dose of IV-TXA (1 g) for 3 h (group A); two doses of IV-TXA (1 g) for 3 and 6 h (group B); or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group C) postoperatively. TKA with a tourniquet was performed by the same surgical team. The primary outcomes were total blood cell loss (TBL), hidden blood loss (HBL), maximum hemoglobin (Hb) drop, and transfusion rate. Secondary outcomes were levels of C-reactive protein (CRP) and D-dimer, and the incidence of postoperative complications. One-way analysis of variance, subgroup analysis, and multivariate correlation analysis were used to calculate the differences among the three groups. RESULTS The study included 56 male and 244 female patients aged 60-80 years. The mean TBL, the mean HBL, and the maximum Hb drop in group C (471.2 ± 190.6 mL, 428.4 ± 190.3 mL, and 21.2 ± 3.8 g/L, respectively) were significantly lower than those in groups B (563.4 ± 224.6 mL, P = 0.030; 519.9 ± 226.4 mL, P = 0.033; and 23.2 ± 4.1 g/L, P = 0.001, respectively), and A (651.6 ± 254.1 mL, P < 0.001; 607.1 ± 254.3 mL, P < 0.001; and 25.1 ± 4.3 g/L, P < 0.001, respectively). No transfusions were required. The postoperative acute inflammatory reaction was less problematic for patients in Group C, and the incidence of thromboembolic events was similar among the groups (P > 0.05). In addition, there were positive correlations between the HBL and the tourniquet inflation time (r = 0.844, P < 0.001). Similarly, the level of CRP on POD1 (r = 0.393, P < 0.001) and POD3 (r = 0.149, P = 0.010), and the level of D-dimer on POD1 (r = 0.382, P < 0.001) were positively correlated with the HBL. CONCLUSION Three doses of postoperative IV-TXA decreased blood loss and diminished the postoperative inflammatory and fibrinolytic response more than a single dose or two doses in elderly patients following TKA without increasing the incidence of adverse events.
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Multiple intravenous tranexamic acid doses in total knee arthroplasty in patients with rheumatoid arthritis: a randomized controlled study
Kang BX, Xu H, Gao CX, Zhong S, Zhang J, Xie J, Sun ST, Ma YH, Xu XR, Zhao C, et al
BMC musculoskeletal disorders. 2021;22(1):425
Abstract
BACKGROUND We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA). METHODS For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay. RESULTS The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P < 0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05). CONCLUSION In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA. TRIAL REGISTRATION The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).
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Intravenous versus oral omeprazole on patients with high risk bleeding peptic ulcers: A prospective randomized clinical trial protocol
Zhang J, Diao P, Zhang L
Medicine. 2021;100(14):e25136
Abstract
BACKGROUND Proton pump inhibitors (PPIs) decrease the rate of rebleeding following endoscopic hemostatic therapy in patients with bleeding peptic ulcers. This study compares the efficacy of oral omeprazole vs intravenous omeprazole in decrease of rebleeding of peptic ulcer patients. METHOD The present study was authorized by the local research ethics committee of Jiangjin District Central Hospital (2020120987) and informed consent was obtained from all patients. All adult patients who were admitted to medical emergency rooms of Jiangjin District Central Hospital due to upper gastrointestinal bleeding (as evidenced by hematemesis, melena or hematochezia) were considered for inclusion in the study. Endoscopy was performed within 24 hours after admission. Patients older than 18 years with successful endoscopic therapy of high risk ulcers [defined as active bleeding (Forrest IA, IB), non-bleeding visible vessel (NBVV, Forrest IIA) or adherent clots (Forrest IIB)] were enrolled. Patients with low risk ulcers (clean base, ulcers with a simple washable clot), suspicious malignant ulcer, bleeding tendency, uremia, liver cirrhosis, Mallory Weiss tear or already on PPI as an outpatient were excluded from study. All were managed endoscopically by injecting 5-30 ml of epinephrine (diluted 1:10000) around the ulcer crater. Cavitations or flattening of bleeding vessel and disappearance of NBVV was considered as established homeostasis. A biopsy was taken from antrum for evaluating Helicobacter pylori infection. Patient with unsuccessful endoscopic therapy were not enrolled and were referred to general surgeon. Information on demography, history of previous upper gastrointestinal bleeding, NSAID or ASA ingestion, ulcer location, bleeding stigmata and blood transfusion volume at entry were recorded in all patients. In the oral omeprazole group, the patients received 40 mg omeprazole orally twice daily for 72 hours. In intravenous omeprazole group, they received omeprazole 80 mg bolus and then 8 mg/hour infusion for 48-72 hours. Then, all patients received omeprazole 20 mg orally for 30 days. On the day of discharge Helicobacter pylori infected patients received standard regimens. RESULTS Figure 1 showed the primary and secondary end points. DISCUSSION Intravenous administration of PPIs has limitations. They are expensive, require a dedicated intravenous line, need nursing supervision and hospital admission. So, it would be reasonable to prescribe oral PPIs to patients with high risk bleeding ulcers provided that it is as effective as its intravenous counterpart. Oral PPIs have a high bioavailability. Its effect initiates one hour after ingestion and the maximal plasma concentration is achieved after 2-3 hours. However, there are few studies comparing oral and intravenous PPI in decreasing risk of rebleeding in peptic ulcer patients. More high quality randomized controlled trials are still necessary. REGISTRATION NUMBER researchregistry 6588.
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Hemoglobin Concentration May Affect the Effect of Atorvastin on Chronic Subdural Hematoma After Burr-Hole Drainage at High Altitude
Wei L, Lin C, Zhong M, Zhang J, Zhu G
Front Neurosci. 2020;14:503
Abstract
Objective: Chronic subdural hematoma (CSDH) is a common disease. Atorvastatin calcium can increase CSDH absorption. However, whether atorvastatin can increase hematoma absorption and reduce recurrence at high altitudes is not clear. Methods: After burr-hole drainage, CSDH patients were divided into an atorvastatin group and a control group. Follow-up computed tomography (CT) was performed on day 1, months 1, 2, and 3 after surgery. Then, the recurrence rate, poor therapeutic effect, time to recurrence, poor surgical result, recurrence with operation, CSDH volume, and Markwalder grading scale score (MGSS) were calculated, and related risk factors were analyzed. Results: The non-recurrent and recurrent patients in the control group differed significantly in terms of the hemoglobin concentration (HB) [176.24 +/- 16.43 vs. 194.25 +/- 12.34 (g/L), p < 0.01], CT value [41.92 +/- 10.76 vs. 34.12 +/- 8.78 (Hu), p < 0.01], and low-density time [3.88 +/- 1.04 vs. 5.50 +/- 0.87 (d), p < 0.01]. The non-recurrent and recurrent patients in the atorvastatin group differed significantly in terms of the HB [172.66 +/- 16.41 vs. 190.45 +/- 10.23 (g/L), p < 0.01], CT value [38.91 +/- 7.16 vs. 29.50 +/- 8.61 (Hu), p < 0.01], and mixed [2 vs. 4 (n), p < 0.05] and low-density time [4.09 +/- 0.75 vs. 5.45 +/- 1.12 (d), p < 0.01]. The logistic regression analysis showed that HB [odds ratio, 1.14; 95% confidence interval (CI), 1.04-1.25 in the control group, odds ratio, 1.13; 95% CI, 1.03-1.23 in the atorvastatin group] and low-density time (odds ratio, 3.53; 95% CI, 1.42-8.74 in the control group, odds ratio, 2.53; 95% CI, 1.10-5.80 in the atorvastatin group) were possible risk factors for the two groups. The receiver operating characteristic curves showed that the area under the receiver operating characteristic curve values for the HB, CT value (Hu), and low-density time were 0.812, 0.702, and 0.755 for all subjects; 0.812, 0.719, and 0.790 for the control group; and 0.807, 0.682, and 0.756 for the atorvastatin group, respectively. The postoperative follow-up results showed that there was no significant difference in the recurrence rate, poor therapeutic effect, time to recurrence, poor surgical result, recurrence with operation, CSDH volume, or MGSS between the two groups. Conclusion: The effect of atorvastatin was not significant after the operation. The risk factors for CSDH recurrence were the HB and low-density time. The HB was the most specific and sensitive predictor of CSDH recurrence.
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A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent beta-Thalassemia
Cappellini MD, Viprakasit V, Taher AT, Georgiev P, Kuo KHM, Coates T, Voskaridou E, Liew HK, Pazgal-Kobrowski I, Forni GL, et al
N Engl J Med. 2020;382(13):1219-1231
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Editor's Choice
Abstract
BACKGROUND Patients with transfusion-dependent beta-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor beta superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent beta-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 mug per liter (95% confidence interval, -517 to -179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo. CONCLUSIONS The percentage of patients with transfusion-dependent beta-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. (Funded by Celgene and Acceleron Pharma; BELIEVE ClinicalTrials.gov number, NCT02604433; EudraCT number, 2015-003224-31.).
PICO Summary
Population
Adults with transfusion-dependent beta-thalassemia (n= 336).
Intervention
Luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) for at least 48 weeks (n=224).
Comparison
Placebo for at least 48 weeks (n= 112).
Outcome
The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group, as was the percentage of those who had a reduction of at least 50%. The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 mug per liter in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo.