最近的研究表明,在生理盐水鼻腔冲洗(SNI)中添加茶碱可以有效治疗病毒后嗅觉功能障碍(OD),在COVID-19大流行期间,人们对公共卫生的关注日益增加。
与安慰剂相比,评估SNI中添加茶碱对COVID-19相关OD的疗效和安全性。
这个三盲,安慰剂对照,2期随机临床试验几乎在2021年3月15日至8月31日之间进行.居住在密苏里州或伊利诺伊州的成年人在这段时间内被招募,如果他们在疑似COVID-19感染后OD持续3至12个月。数据分析于2021年10月至12月进行。
将盐水窦冲洗试剂盒和装有400毫克茶碱(治疗)或500毫克乳糖粉(对照)的外观相同的胶囊瓶邮寄给同意的研究参与者。指示参与者将胶囊内容物溶解在盐水冲洗液中,并在早晨和晚上使用该溶液冲洗鼻腔6周。
主要结果是治疗组和对照组之间的应答率差异,定义为治疗后临床总体印象改善量表的改善至少略好。次要结果指标包括宾夕法尼亚大学气味识别测试(UPSIT)的变化,嗅觉障碍问卷,全面健康36项简式健康调查,和COVID-19相关问题。
共有51名参与者参加了这项研究;平均(SD)年龄为46.0(13.1)岁,36名(71%)参与者为女性。参与者被随机分配到SNI与茶碱(n=26)或SNI与安慰剂(n=25)。45名参与者完成了这项研究。在治疗结束时,茶碱组的13名(59%)参与者报告说,与安慰剂组的10名(43%)相比,临床总体印象-改善量表(响应者)至少略有改善(绝对差异,15.6%;95%CI,-13.2%至44.5%)。基线和6周之间UPSIT变化的中位数差异在茶碱组的参与者中为3.0(95%CI,-1.0至7.0),在安慰剂组的参与者中为0.0(95%CI,-2.0至6.0)。混合模型分析显示,通过研究评估的UPSIT得分的变化在两个研究组之间没有统计学上的显着差异。茶碱组的11名(50%)参与者和安慰剂组的6名(26%)参与者从基线到6周的UPSIT评分变化了4个或更多个点。通过UPSIT测量的应答者比率的差异为24%(95%CI,-4%至52%),有利于茶碱。
这项随机临床试验表明,茶碱鼻腔冲洗对COVID-19相关OD参与者嗅觉的临床益处尚无定论,尽管是由主观评估提出的。需要更大规模的研究来更全面地研究这种治疗的疗效。
ClinicalTrials.gov标识符:NCT04789499。
Recent studies suggest that theophylline added to saline nasal irrigation (SNI) can be an effective treatment for postviral olfactory dysfunction (OD), a growing public health concern during the COVID-19 pandemic.
To evaluate the efficacy and safety of theophylline added to SNI compared with placebo for COVID-19-related OD.
This triple-blinded, placebo-controlled, phase 2 randomized clinical
trial was conducted virtually between March 15 and August 31, 2021. Adults residing in Missouri or Illinois were recruited during this time period if they had OD persisting for 3 to 12 months following suspected COVID-19 infection. Data analysis was conducted from October to December 2021.
Saline sinus rinse kits and bottles of identical-appearing capsules with either 400 mg of theophylline (treatment) or 500 mg of lactose powder (control) were mailed to consenting
study participants. Participants were instructed to dissolve the capsule contents into the saline rinse and use the solution to irrigate their nasal cavities in the morning and at night for 6 weeks.
The primary outcome was the difference in the rate of responders between the treatment and the control arms, defined as a response of at least slightly better improvement in the Clinical Global Impression-Improvement scale posttreatment. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT), the Questionnaire for Olfactory Disorders, the 36-Item Short Form Health Survey on general health, and COVID-19-related questions.
A total of 51 participants were enrolled in the study; the mean (SD) age was 46.0 (13.1) years, and 36 (71%) participants were women. Participants were randomized to SNI with theophylline (n = 26) or to SNI with placebo (n = 25). Forty-five participants completed the
study. At the end of treatment, 13 (59%) participants in the theophylline arm reported at least slight improvement in the Clinical Global Impression-Improvement scale (responders) compared with 10 (43%) in the placebo arm (absolute difference, 15.6%; 95% CI, -13.2% to 44.5%). The median difference for the UPSIT change between baseline and 6 weeks was 3.0 (95% CI, -1.0 to 7.0) for participants in the theophylline arm and 0.0 (95% CI, -2.0 to 6.0) for participants in the placebo arm. Mixed-model analysis revealed that the change in UPSIT scores through study assessments was not statistically significantly different between the 2
study arms. Eleven (50%) participants in the theophylline arm and 6 (26%) in the placebo arm had a change of 4 or more points in UPSIT scores from baseline to 6 weeks. The difference in the rate of responders as measured by the UPSIT was 24% (95% CI, -4% to 52%) in favor of theophylline.
This randomized clinical
trial suggests that the clinical benefit of
theophylline nasal irrigations on olfaction in participants with COVID-19-related OD is inconclusive, though suggested by subjective assessments. Larger studies are warranted to investigate the efficacy of this treatment more fully.
ClinicalTrials.gov Identifier: NCT04789499.