Radiology Department, Hospital Naval Almirante Nef, Subida Alesandri S/N., 254000, Viña del Mar, Provincia de Valparaíso, Chile.
Radiology Department, Hospital Dr. Eduardo Pereira, Valparaiso, Chile.
Crit Care. 2022 Jan 3;26(1):1. doi: 10.1186/s13054-021-03885-y.
SARS-CoV-2 seems to affect the regulation of pulmonary perfusion. Hypoperfusion in areas of well-aerated lung parenchyma results in a ventilation-perfusion mismatch that can be characterized using subtraction computed tomography angiography (sCTA). This study aims to evaluate the efficacy of oral sildenafil in treating COVID-19 inpatients showing perfusion abnormalities in sCTA.
Triple-blinded, randomized, placebo-controlled trial was conducted in Chile in a tertiary-care hospital able to provide on-site sCTA scans and ventilatory support when needed between August 2020 and March 2021. In total, 82 eligible adults were admitted to the ED with RT-PCR-confirmed or highly probable SARS-COV-2 infection and sCTA performed within 24 h of admission showing perfusion abnormalities in areas of well-aerated lung parenchyma; 42 were excluded and 40 participants were enrolled and randomized (1:1 ratio) once hospitalized. The active intervention group received sildenafil (25 mg orally three times a day for seven days), and the control group received identical placebo capsules in the same way. Primary outcomes were differences in oxygenation parameters measured daily during follow-up (PaO/FiO ratio and A-a gradient). Secondary outcomes included admission to the ICU, requirement of non-invasive ventilation, invasive mechanical ventilation (IMV), and mortality rates. Analysis was performed on an intention-to-treat basis.
Totally, 40 participants were enrolled (20 in the placebo group and 20 in the sildenafil group); 33 [82.5%] were male; and median age was 57 [IQR 41-68] years. No significant differences in mean PaO/FiO ratios and A-a gradients were found between groups (repeated-measures ANOVA p = 0.67 and p = 0.69). IMV was required in 4 patients who received placebo and none in the sildenafil arm (logrank p = 0.04). Patients in the sildenafil arm showed a significantly shorter median length of hospital stay than the placebo group (9 IQR 7-12 days vs. 12 IQR 9-21 days, p = 0.04).
No statistically significant differences were found in the oxygenation parameters. Sildenafil treatment could have a potential therapeutic role regarding the need for IMV in COVID-19 patients with specific perfusion patterns in sCTA. A large-scale study is needed to confirm these results.
Sildenafil for treating patients with COVID-19 and perfusion mismatch: a pilot randomized trial, NCT04489446, Registered 28 July 2020, https://clinicaltrials.gov/ct2/show/NCT04489446 .
SARS-CoV-2 似乎会影响肺灌注的调节。通气/灌注不匹配在充气良好的肺实质区域出现低灌注，可通过减影 CT 血管造影（sCTA）进行特征描述。本研究旨在评估口服西地那非治疗 sCTA 显示灌注异常的 COVID-19 住院患者的疗效。
2020 年 8 月至 2021 年 3 月，在智利的一家三级保健医院进行了一项三盲、随机、安慰剂对照试验，该医院能够在住院后 24 小时内提供现场 sCTA 扫描和需要时的通气支持。共纳入 82 名因 RT-PCR 确诊或高度疑似 SARS-COV-2 感染而入住急诊的合格成年人，并在入院后 24 小时内进行 sCTA 检查，显示充气良好的肺实质区域存在灌注异常；排除 42 例后，40 例参与者入组并随机（1:1 比例）。干预组接受西地那非（25mg 口服，每日 3 次，共 7 天），对照组给予相同的安慰剂胶囊。主要结局为每日随访时氧合参数的差异（PaO/FiO 比值和 A-a 梯度）。次要结局包括入住 ICU、需要无创通气、有创机械通气（IMV）和死亡率。分析采用意向治疗。
共纳入 40 名参与者（安慰剂组 20 名，西地那非组 20 名）；33 名[82.5%]为男性；中位年龄为 57[IQR 41-68]岁。两组间平均 PaO/FiO 比值和 A-a 梯度无显著差异（重复测量方差分析 p=0.67 和 p=0.69）。接受安慰剂的 4 例患者需要 IMV，而西地那非组无患者需要（logrank p=0.04）。西地那非组的中位住院时间明显短于安慰剂组（9 IQR 7-12 天 vs. 12 IQR 9-21 天，p=0.04）。
两组间氧合参数无统计学差异。西地那非治疗可能对 sCTA 显示特定灌注模式的 COVID-19 患者有潜在的治疗作用，需要 IMV。需要一项大规模研究来证实这些结果。
西地那非治疗 COVID-19 与灌注不匹配患者的试验：一项随机试验，NCT04489446，2020 年 7 月 28 日注册，https://clinicaltrials.gov/ct2/show/NCT04489446。
