1.
A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia
Mei H, Liu X, Li Y, Zhou H, Feng Y, Gao G, Cheng P, Huang R, Yang L, Hu J, et al
Journal of hematology & oncology. 2021;14(1):37
Abstract
BACKGROUND Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients. METHODS Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 10(9)/L) after 8 weeks of treatment. RESULTS The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83-68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39-86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment. CONCLUSIONS In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.
2.
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.
3.
The BELIEVE Trial: Results of a Phase 3,Randomised, Double-Blind, Placebo-ControlledStudy of Luspatercept in Adult b-ThalassaemiaPatients Who Require Regular Red Blood Cell(RBC) Transfusions
Porter J, Shah F, Drasar E, Hill QA, Telfer P, Viprakasit V, Taher A, Georgiev P, Kuo KHM, Coates T, et al
British Journal of Haematology. 2019;185(S1):112.. BSH19-PO-124.
4.
A prospective study of platelet-rich plasma as biological augmentation for acute achilles tendon rupture repair
Zou J, Mo X, Shi Z, Li T, Xue J, Mei G, Li X
Biomed Research International. 2016;2016:9364170.
Abstract
Acute Achilles tendon rupture is one of the most common tendon injuries in adults. We hypothesized that Platelet-Rich Plasma (PRP) can be used as biological augmentation for surgical treatment of acute Achilles tendon rupture. Our study is a prospective randomized controlled trial. Patients with acute Achilles tendon rupture undergoing surgical repair were randomly assigned into either control group or PRP group. End-to-end modified Krackow suture was performed in both groups. In the PRP group, PRP was injected into the paratenon sheath and around the ruptured tissue after the tendon was repaired. Postoperatively we evaluated isokinetic muscle strength at 3, 6, 12, and 24 months. In addition, ankle ROM, calf circumference, Leppilahti score, and the SF-36 score were evaluated at 6, 12, and 24 months after operation. At 3 months, the PRP group had better isokinetic muscle. The PRP group also achieved higher SF-36 and Leppilahti scores at 6 and 12 months. At 24 months, the PRP group had an improved ankle range of motion compared to the control group. Our study results suggest that PRP can serve as a biological augmentation to acute Achilles tendon rupture repair and improves both short and midterm functional outcomes.