The New England journal of medicine
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Randomized Controlled Trial Multicenter Study
Mitapivat versus Placebo for Pyruvate Kinase Deficiency.
Pyruvate kinase deficiency is a rare, hereditary, chronic condition that is associated with hemolytic anemia. In a phase 2 study, mitapivat, an oral, first-in-class activator of erythrocyte pyruvate kinase, increased the hemoglobin level in patients with pyruvate kinase deficiency. ⋯ In patients with pyruvate kinase deficiency, mitapivat significantly increased the hemoglobin level, decreased hemolysis, and improved patient-reported outcomes. No new safety signals were identified in the patients who received mitapivat. (Funded by Agios Pharmaceuticals; ACTIVATE ClinicalTrials.gov number, NCT03548220.).
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Randomized Controlled Trial Multicenter Study
Nonoperative or Surgical Treatment of Acute Achilles' Tendon Rupture.
Whether surgical repair of an acute Achilles' tendon rupture by an open-repair or minimally invasive approach is associated with better outcomes than nonsurgical treatment is not clear. ⋯ In patients with Achilles' tendon rupture, surgery (open repair or minimally invasive surgery) was not associated with better outcomes than nonoperative treatment at 12 months. (Funded by the South-Eastern Norway Regional Health Authority and Akershus University Hospital; ClinicalTrials.gov number, NCT01785264.).
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Rilzabrutinib, an oral, reversible covalent inhibitor of Bruton's tyrosine kinase, may increase platelet counts in patients with immune thrombocytopenia by means of dual mechanisms of action: decreased macrophage (Fcγ receptor)-mediated platelet destruction and reduced production of pathogenic autoantibodies. ⋯ Rilzabrutinib was active and associated with only low-level toxic effects at all dose levels. The dose of 400 mg twice daily was identified as the dose for further testing. Overall, rilzabrutinib showed a rapid and durable clinical activity that improved with length of treatment. (Funded by Sanofi; ClinicalTrials.gov number, NCT03395210; EudraCT number, 2017-004012-19.).
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Randomized Controlled Trial
Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19.
Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (Mpro) inhibitor with potent pan-human-coronavirus activity in vitro. ⋯ Treatment of symptomatic Covid-19 with nirmatrelvir plus ritonavir resulted in a risk of progression to severe Covid-19 that was 89% lower than the risk with placebo, without evident safety concerns. (Supported by Pfizer; ClinicalTrials.gov number, NCT04960202.).