泼尼松龙和维生素 B1、B6、B12 治疗 COVID-19 后综合征患者的可行性、安全性和有效性（PreVitaCOV）：一项在初级保健中进行的随机、双盲、安慰剂对照多中心试验（IIIb 期）的方案。

Feasibility, safety and effectiveness of prednisolone and vitamin B1, B6, and B12 in patients with post-COVID-19-syndrome (PreVitaCOV) - protocol of a randomised, double-blind, placebo-controlled multicentre trial in primary care (phase IIIb).

机构信息

Department of General Practice, University Hospital Würzburg, Josef-Schneider-Straße 2, Building D7, 97080, Würzburg, Germany.

Institute of General Practice and Interprofessional Care, University Hospital Tübingen, Osianderstrasse 5, 72076, Tübingen, Germany.

出版信息

BMC Infect Dis. 2024 Jan 6;24(1):56. doi: 10.1186/s12879-023-08925-2.

DOI:10.1186/s12879-023-08925-2

PMID:38184567

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10771676/

Abstract

BACKGROUND

After infection with SARS-CoV-2 a relevant proportion of patients complains about persisting symptoms, a condition termed Post-COVID-19-syndrome (PC19S). So far, possible treatments are under investigation. Among others, neurotropic vitamins and anti-inflammatory substances are potential options. Thus, the PreVitaCOV trial aims to assess feasibility, safety, and effectiveness of treating patients in primary care with prednisolone and/or vitamin B1, B6 and B12.

METHODS

The phase IIIb, multi-centre randomised, double-blind, and placebo-controlled PreVitaCOV trial has a factorial design and is planned as a two-phase approach. The pilot phase assessed feasibility and safety and was transformed into a confirmatory phase to evaluate effectiveness since feasibility was proven. Adult patients with PC19S after a documented SARS-CoV-2 infection at least 12 weeks ago are randomly assigned to 4 parallel treatments: prednisolone 20 mg for five days followed by 5 mg for 23 days (trial drug 1), B vitamins (B1 (100 mg OD), B6 (50 mg OD), and B12 (500 µg OD)) for 28 days (trial drug 2), trial drugs 1 and 2, or placebo. The primary outcome of the pilot phase was defined as the retention rate of the first 100 patients. Values of ≥ 85% were considered as confirmation of feasibility, this criterion was even surpassed by a retention rate of 98%. After transformation, the confirmatory phase proceeds by enrolling 240 additional patients. The primary outcome for the study is the change of symptom severity from baseline to day 28 as assessed by a tailored Patient Reported Outcomes Measurement Information System (PROMIS) total score referring to five symptom domains known to be typical for PC19S (fatigue, dyspnoea, cognition, anxiety, depression). The confirmatory trial is considered positive if superiority of any treatment is demonstrated over placebo operationalised by an improvement of at least 3 points on the PROMIS total score (t-score).

DISCUSSION

The PreVitaCOV trial may contribute to the understanding of therapeutic approaches in PC19S in a primary care context.

TRIAL REGISTRATION

EudraCT: 2022-001041-20. DRKS: DRKS00029617.

CLINICALTRIALS

gov: F001AM02222_1 (registered: 05 Dec 2022).

摘要

背景

感染 SARS-CoV-2 后，相当一部分患者会出现持续症状，这种情况被称为新冠后综合征（PC19S）。到目前为止，正在对可能的治疗方法进行研究。其中，神经营养维生素和抗炎物质是潜在的选择。因此，PreVitaCOV 试验旨在评估在初级保健中用泼尼松龙和/或维生素 B1、B6 和 B12 治疗患者的可行性、安全性和有效性。

方法

该 IIIb 期、多中心、随机、双盲、安慰剂对照的 PreVitaCOV 试验采用析因设计，计划分为两阶段进行。初步阶段评估了可行性和安全性，并转化为确证阶段，以评估有效性，因为已经证明了可行性。患有 PC19S 的成年患者，在记录的 SARS-CoV-2 感染后至少 12 周，随机分为 4 种平行治疗：泼尼松龙 20mg 连用 5 天，然后 5mg 连用 23 天（试验药物 1），B 族维生素（B1（100mg OD）、B6（50mg OD）和 B12（500µg OD））连用 28 天（试验药物 2），试验药物 1 和 2，或安慰剂。初步阶段的主要结局定义为前 100 例患者的保留率。保留率≥85%被认为是可行性的确认，保留率甚至超过了 98%。转化后，确证阶段将招募 240 名额外患者。研究的主要结局是通过定制的患者报告结局测量信息系统（PROMIS）总分评估 5 个症状领域的症状严重程度从基线到第 28 天的变化，这 5 个症状领域是 PC19S 的典型症状（疲劳、呼吸困难、认知、焦虑、抑郁）。如果任何治疗的疗效优于安慰剂（以 PROMIS 总分至少改善 3 分来表示），则认为确证试验为阳性（t 评分）。