Abstract：
OBJECTIVE: The PARACOR-19 randomized controlled trial (RCT) was designed to examine the effects of sacubitril/valsartan on markers of cardiac injury, inflammation, structure, and function among patients who have recovered from acute coronavirus disease 2019 (COVID-19) infection.
RESULTS: PARACOR-19 was a single-centre, double-blind RCT of patients with cardiovascular risk factors and a history of COVID-19 infection 4-16 weeks prior to enrolment. Patients were randomized to sacubitril/valsartan (titrated to the maximum dose of 97/103 mg twice daily) versus matching placebo. Co-primary endpoints were change from baseline to 12 weeks in high-sensitivity cardiac troponin T (hs-cTnT) and soluble ST2 (sST2). Exploratory endpoints included change from baseline to 12 weeks in additional circulating biomarkers. Overall, 42 patients were randomized between August 2021 and March 2023 (n = 20 sacubitril/valsartan, n = 22 placebo). Median (25th-75th) time from COVID-19 diagnosis to enrolment was 67 (48-80) days. Median age was 67 (62-71) years, 48% were female, and 91% were White. Compared with placebo, sacubitril/valsartan did not have a significant effect on the co-primary endpoints of change from baseline in hs-TnT and sST2 (all p ≥ 0.29). In exploratory analyses, sacubitril/valsartan led to a 46% greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and 51% greater reduction in C-terminal telopeptide of collagen type I (CITP). Permanent drug discontinuation occurred in four patients in the sacubitril/valsartan group and three patients in the placebo group. There were no deaths and one patient was hospitalized in each group.
CONCLUSIONS: In this pilot RCT of patients who recovered from acute COVID-19, sacubitril/valsartan did not lower hs-cTnT or sST2 compared with placebo. Exploratory analyses suggested potential benefits of sacubitril/valsartan on cardiac wall stress and collagen turnover as measured by NT-proBNP and CITP. Sacubitril/valsartan was well tolerated.
BACKGROUND: ClinicalTrials.gov NCT04883528.
RESULTS: PARACOR-19 was a single-centre, double-blind RCT of patients with cardiovascular risk factors and a history of COVID-19 infection 4-16 weeks prior to enrolment. Patients were randomized to sacubitril/valsartan (titrated to the maximum dose of 97/103 mg twice daily) versus matching placebo. Co-primary endpoints were change from baseline to 12 weeks in high-sensitivity cardiac troponin T (hs-cTnT) and soluble ST2 (sST2). Exploratory endpoints included change from baseline to 12 weeks in additional circulating biomarkers. Overall, 42 patients were randomized between August 2021 and March 2023 (n = 20 sacubitril/valsartan, n = 22 placebo). Median (25th-75th) time from COVID-19 diagnosis to enrolment was 67 (48-80) days. Median age was 67 (62-71) years, 48% were female, and 91% were White. Compared with placebo, sacubitril/valsartan did not have a significant effect on the co-primary endpoints of change from baseline in hs-TnT and sST2 (all p ≥ 0.29). In exploratory analyses, sacubitril/valsartan led to a 46% greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and 51% greater reduction in C-terminal telopeptide of collagen type I (CITP). Permanent drug discontinuation occurred in four patients in the sacubitril/valsartan group and three patients in the placebo group. There were no deaths and one patient was hospitalized in each group.
CONCLUSIONS: In this pilot RCT of patients who recovered from acute COVID-19, sacubitril/valsartan did not lower hs-cTnT or sST2 compared with placebo. Exploratory analyses suggested potential benefits of sacubitril/valsartan on cardiac wall stress and collagen turnover as measured by NT-proBNP and CITP. Sacubitril/valsartan was well tolerated.
BACKGROUND: ClinicalTrials.gov NCT04883528.
摘要：
目的：PARACOR-19随机对照试验（RCT）旨在研究沙库巴曲/缬沙坦对心脏损伤标志物的影响，炎症,结构,和从2019年急性冠状病毒病（COVID-19）感染中恢复的患者的功能。
结果：PARACOR-19是单中心，纳入前4-16周对有心血管危险因素且有COVID-19感染史的患者进行双盲RCT。与匹配的安慰剂相比，患者被随机分配给沙库巴曲/缬沙坦（每日两次滴定至最大剂量97/103mg）。共同主要终点是高敏心肌肌钙蛋白T（hs-cTnT）和可溶性ST2（sST2）从基线到12周的变化。探索性终点包括其他循环生物标志物从基线到12周的变化。总的来说,42例患者在2021年8月至2023年3月之间随机分组(n=20沙库巴曲/缬沙坦，n=22安慰剂)。从COVID-19诊断到登记的中位时间（第25-75天）为67天（48-80天）。年龄中位数为67（62-71）岁，48%是女性,91%是白人。与安慰剂相比，沙库巴曲/缬沙坦对hs-TnT和sST2从基线变化的共同主要终点没有显著影响(所有p≥0.29).在探索性分析中，沙库巴曲/缬沙坦导致I型胶原蛋白的N末端B型利钠肽前体（NT-proBNP）降低了46％，C末端端肽降低了51％。沙库巴曲/缬沙坦组的四名患者和安慰剂组的三名患者永久停药。无死亡病例，每组1例患者住院。
结论：在这项从急性COVID-19康复的患者的试验RCT中，沙库巴曲/缬沙坦与安慰剂相比没有降低hs-cTnT或sST2。探索性分析表明，通过NT-proBNP和CITP测量，沙库巴曲/缬沙坦对心脏壁压力和胶原更新的潜在益处。Sacubitril/缬沙坦耐受性良好。
背景：ClinicalTrials.govNCT04883528。
结果：PARACOR-19是单中心，纳入前4-16周对有心血管危险因素且有COVID-19感染史的患者进行双盲RCT。与匹配的安慰剂相比，患者被随机分配给沙库巴曲/缬沙坦（每日两次滴定至最大剂量97/103mg）。共同主要终点是高敏心肌肌钙蛋白T（hs-cTnT）和可溶性ST2（sST2）从基线到12周的变化。探索性终点包括其他循环生物标志物从基线到12周的变化。总的来说,42例患者在2021年8月至2023年3月之间随机分组(n=20沙库巴曲/缬沙坦，n=22安慰剂)。从COVID-19诊断到登记的中位时间（第25-75天）为67天（48-80天）。年龄中位数为67（62-71）岁，48%是女性,91%是白人。与安慰剂相比，沙库巴曲/缬沙坦对hs-TnT和sST2从基线变化的共同主要终点没有显著影响(所有p≥0.29).在探索性分析中，沙库巴曲/缬沙坦导致I型胶原蛋白的N末端B型利钠肽前体（NT-proBNP）降低了46％，C末端端肽降低了51％。沙库巴曲/缬沙坦组的四名患者和安慰剂组的三名患者永久停药。无死亡病例，每组1例患者住院。
结论：在这项从急性COVID-19康复的患者的试验RCT中，沙库巴曲/缬沙坦与安慰剂相比没有降低hs-cTnT或sST2。探索性分析表明，通过NT-proBNP和CITP测量，沙库巴曲/缬沙坦对心脏壁压力和胶原更新的潜在益处。Sacubitril/缬沙坦耐受性良好。
背景：ClinicalTrials.govNCT04883528。
