Food Security Research Center, Isfahan University of Medical Sciences, PO Box: 00983117922110, Isfahan, Iran.
Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Trials. 2021 Jul 6;22(1):434. doi: 10.1186/s13063-021-05372-9.
This study aims to investigate the efficacy of curcumin-piperine co-supplementation on oxidative stress factors, clinical symptoms, and mortality rate in patients with coronavirus (COVID-19) admitted to the intensive care unit (ICU).
This study is a randomized, placebo-controlled, double-blind, parallel-arm clinical trial.
The study participants will be recruited from patients admitted to the ICU of Al-Zahra hospital with a definitive diagnosis of COVID-19. The inclusion criteria are aged between 20 and 75 years, confirmation of COVID-19 based on the PCR test, and admitted to the ICU. The exclusion criteria include the present use of parenteral nutrition support, a history of underlying diseases such as congenital disorders, immune diseases, renal and hepatic insufficiency, and pancreatitis, a history of sensitivity to herbal remedies such as turmeric and pepper, and regular use of anticoagulant drugs such as warfarin. This study will be performed in the Al-Zahra hospital, an academic hospital affiliated with Isfahan University of Medical Sciences, Isfahan, Iran.
Sixty eligible patients will be randomly assigned, in a 1:1 ratio, to receive curcumin-piperine capsules (three capsules/day; each capsules containing 500 mg curcumin plus 5 mg piperine; in total 1500 mg curcumin and 15 mg piperine/daily) for seven days (n=30) or matching placebo capsules (three capsules/day; each capsules containing 505 mg maltodextrin; totally 1515 mg, maltodextrin/ daily) for same duration (n=30). Capsules will be administered after oral or enteral feeding at 9, 15 and 21 o'clock.
The primary outcome is the time from initiation of supplementation (curcumin-piperine or placebo) to normalization of fever, respiratory rate, and blood oxygen saturation. The secondary outcomes are the mortality rate, length of stay in ICU, temperature, levels of blood oxygen saturation, ventilator dependency, respiratory rate, levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), levels of liver markers (ALT, AST, LDH), and levels of kidney function markers (BUN, Creatinine).
All of the parameters will be assessed at baseline and end of the study (7 days intervention). In addition, the rate of mortality will be collected after 4 weeks (28 days' mortality in the ICU, 4 weeks follow up).
Eligible patients will be randomly assigned to either the intervention group (Curcumin-piperine) or the control group (Placebo). Randomization sequences will be generated using an electronic table of random numbers to allocate the included participants into either control or intervention groups (in a 1:1 ratio) using the stratified block randomization method. Stratification was conducted according to sex (male and female), with a block size of four. The allocation sequences will be prepared by an independent statistician and will be kept inside sealed, opaque, and consecutively numbered envelopes. Participants, investigators, nurses, and physicians will be unaware of the trial-group assignment.
BLINDING (MASKING): This study is a double-blind clinical trial (participants, investigators, nurses, and physicians). The curcumin-piperine and placebo supplements will be similar in the terms of texture, taste, color, odor, and weight. Both tablets will be provided in containers that are completely identical in weight, shape, labeling, and packaging. All participants, investigators, nurses, and physicians will be unaware of the trial-group assignment.
NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is estimated at 60 participants, including 30 patients in the intervention group and 30 patients in the placebo group.
The protocol is Version 2, registered on May 13, 2021. Recruitment began May 20, 2021, and is anticipated to be completed by September 20, 2021.
This trial has been registered in Iranian Registry of Clinical Trials (IRCT) with the title of "Evaluation of the effect of curcumin-piperine supplementation in patients with coronavirus admitted to the intensive care unit (ICU): a double-blind clinical trial study". IRCT registration number is IRCT20121216011763N52 . The registration date was May 13, 2021.
The full protocol is attached as an additional file, accessible from the Trials website (File 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
本研究旨在探讨姜黄素-胡椒碱联合补充对重症监护病房（ICU）中 COVID-19 患者氧化应激因素、临床症状和死亡率的疗效。
这是一项随机、安慰剂对照、双盲、平行臂临床试验。
研究参与者将从 Al-Zahra 医院 ICU 中确诊为 COVID-19 的患者中招募。纳入标准为年龄在 20 至 75 岁之间，基于 PCR 检测确认 COVID-19，并且入住 ICU。排除标准包括目前正在接受肠外营养支持、先天性疾病、免疫疾病、肝肾不全和胰腺炎等基础疾病病史、对草药如姜黄和胡椒敏感的病史、以及经常使用抗凝药物如华法林。这项研究将在伊朗伊斯法罕大学医学科学附属 Al-Zahra 医院进行。
将 60 名符合条件的患者随机分为 1:1 比例，分别接受姜黄素-胡椒碱胶囊（每天 3 粒；每粒含 500 毫克姜黄素加 5 毫克胡椒碱；总计 1500 毫克姜黄素和 15 毫克胡椒碱/天）治疗 7 天（n=30）或匹配的安慰剂胶囊（每天 3 粒；每粒含 505 毫克麦芽糊精；总计 1515 毫克，麦芽糊精/天）治疗相同时间（n=30）。胶囊将在 9 点、15 点和 21 点口服或肠内喂养后服用。
主要结局是从开始补充（姜黄素-胡椒碱或安慰剂）到发热、呼吸频率和血氧饱和度正常化的时间。次要结局是死亡率、ICU 住院时间、体温、血氧饱和度水平、呼吸机依赖、呼吸频率、C 反应蛋白（CRP）水平、红细胞沉降率（ESR）水平、肝标志物（ALT、AST、LDH）水平和肾功能标志物（BUN、肌酐）水平。
所有参数将在基线和研究结束时（7 天干预）进行评估。此外，将在 4 周后（ICU 内 28 天死亡率，4 周随访）收集死亡率。
符合条件的患者将被随机分配到干预组（姜黄素-胡椒碱）或对照组（安慰剂）。使用电子随机数表生成随机序列，以分层块随机化方法将纳入的参与者分为对照组（n=30）或干预组（n=30）（1:1 比例）。分层根据性别（男性和女性）进行，块大小为 4。随机序列将由独立的统计学家准备，并将保存在密封、不透明且连续编号的信封中。参与者、研究者、护士和医生将不知道试验组的分配。
双盲（盲法）：本研究是一项双盲临床试验（参与者、研究者、护士和医生）。姜黄素-胡椒碱和安慰剂补充剂在质地、口感、颜色、气味和重量方面将相似。两种片剂将以完全相同的重量、形状、标签和包装提供。所有参与者、研究者、护士和医生都将不知道试验组的分配。
随机数量（样本量）：样本量估计为 60 名参与者，包括干预组 30 名患者和安慰剂组 30 名患者。
方案为第 2 版，于 2021 年 5 月 13 日注册。招募于 2021 年 5 月 20 日开始，预计于 2021 年 9 月 20 日完成。
该试验已在伊朗临床试验注册中心（IRCT）注册，标题为“姜黄素-胡椒碱补充对入住重症监护病房（ICU）的冠状病毒患者的疗效评估：一项双盲临床试验研究”。IRCT 注册号为 IRCT20121216011763N52。注册日期为 2021 年 5 月 13 日。
完整方案作为附加文件附上，可从试验网站（文件 1）访问。为了加快传播该材料，已消除了熟悉的格式；本函作为完整方案的关键要素摘要。
