A Phase IIb, Double Blind, Placebo-controlled Clinical Study Designed to Evaluate the Effect of CimetrA in Patients Diagnosed With COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Change in WHO Ordinal Scale for clinical improvement
研究概览
简要总结
Multi-center multinational-controlled study in Israel, Brazil, Spain, and South-Africa.
240 adult patients who suffer from moderate COVID-19 infection. Safety will be assessed through collection and analysis of adverse events, blood and urine laboratory assessments and vital signs.
After Screening visit, the study drug will be administrated twice a day morning and evening (every 12 hours) during (day 1 and day 2) The patients will be randomized in 1:1:1 ratio to study drug (CimetrA) in two dosages in addition to Standard of Care - Arm 1, 2 or (Placebo) in addition to Standard of Care- Arm 3.
详细描述
A preparation of CimertA (Botanical Drug), comprising Curcumin, Boswellia, and Vitamin C in a nanoparticular formulation, is proposed as a treatment for the disease associated with the novel corona virus SARS-CoV-2. This initiative is presented under the urgent circumstances of the fulminant pandemic caused by this lethal disease, which is known as COVID-19 and has spread across the globe causing death and disrupting the normal function of modern society. The grounds for the proposal are rooted in existing knowledge on the components and pharmacological features of this formulation and their relevance to the current understanding of the disease process being addressed.
The breakout of a lethal pneumonia in the city of Wuhan, China, towards the end of 2019, has led to the characterization of the new coronavirus related disease COVID-19. Its prominent features include a high rate of person-to-person transmission, a substantial risk of developing a lethal respiratory syndrome and potential failure of additional organs. Risk factors for a life-threatening clinical course have been identified, including advanced age and assorted comorbidities, such as cardiovascular disease, diabetes mellitus, hypertension, cancer. However, individuals devoid of any of the recognized risk factors are not immune to the severe manifestation of the disease and once infected carry a certain risk of mortality which has been calculated in Italy at circa 2%.
CoV is an enveloped, positive-sense single-stranded RNA (ss-RNA) virus belonging to the Coronaviridae family. The severe acute respiratory syndrome associated coronavirus disease 2019 (COVID-19) illness is a syndrome of viral replication in concert with a host inflammatory response. The cytokine storm and viral evasion of cellular immune responses may play an equally important role in the pathogenesis, clinical manifestation, and outcomes of COVID-19. Systemic proinflammatory cytokines and biomarkers are elevated as the disease progresses towards its advanced stages, and correlate with worse chances of survival.
SARS-CoV-2 activates the innate immune system and results in a release of a large number of cytokines, including IL-6, which can increase vascular permeability and cause a migration of fluid and blood cells into the alveoli as well as the consequent symptoms such as dyspnea and respiratory failure. The higher mortality is being linked to the result of ARDS (acute respiratory distress syndrome) aggravation and the tissue damage that can result in organ-failure and/or death.
Serum cytokine levels that are elevated in patients with Covid-19-associated cytokine storm include interleukin-1β, interleukin-6, IP-10, TNF, interferon-γ, macrophage inflammatory protein (MIP) 1α and 1β, and VEGF. Higher interleukin-6 levels are strongly associated with shorter survival. The relative frequencies of circulating activated CD4+ and CD8+ T cells and plasma blasts are increased in Covid-19. In addition to the elevated systemic cytokine levels and activated immune cells, several clinical and laboratory abnormalities, such as elevated CRP and d-dimer levels, hypoalbuminemia, renal dysfunction, and effusions, are also observed in Covid-19, as they are in cytokine storm disorders. Laboratory test results reflecting hyperinflammation and tissue damage were found to predict worsening outcomes in Covid-19.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
This is a double-blind study: neither the participants nor the investigators will be aware of arm allocation of each study participant.
Blindness is important to avoid bias. Monitoring and reporting of the success of blindness are important for the reader's confidence of the trial results. Groups should be marked by capital letter and blindness should maintain throughout the study.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed by PCR test SARS-CoV-2 infection (according to nationally authorized laboratory criteria)
- •Hospitalized patient with COVID-19 of moderate stable or worsening severity not requiring ICU admission (defined by NIH criteria - fever, cough, dyspnea, fast breathing, but no signs of severe pneumonia, including SpO2 ≥ 94% on room air).
- •Age: 18 years old and above.
- •Subjects must be hospitalized
- •Ability to receive treatment by spray into the oral cavity
排除标准
- •Tube feeding or parenteral nutrition.
- •Patients with scores 5 or above per the Ordinal Scale for Clinical Improvement published by the WHO. (i.e., who need oxygen supply beyond use of nozzles or simple mask)
- •Need for admission to ICU during the present hospitalization at any time prior to completion of the recruitment to the study.
- •Any condition which, in the opinion of the Principal Investigator, would prevent full participation in this trial or would interfere with the evaluation of the trial endpoints.
研究组 & 干预措施
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Biochemistry blood test (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Hematology blood test (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: D-Dimer test (coagulation) (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Inflammatory markers (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Vital signs (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: VAS scale (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: WHO Ordinal Score (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: COVID-19-Related Symptoms assessment (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: COVID-19-Impact on Quality-of-Life Questionnaire (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Pregnancy test (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Physical examination (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: PK parameters (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: SARS-CoV-2 test (PCR) (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: ECG (Diagnostic Test)
Arm 1 - CimetrA-1
CimetrA-1, with a total dose containing a combination of Curcumin 40 mg, Boswellia 30 mg and Vitamin C 120 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Treatment administration (twice a day) (Drug)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Biochemistry blood test (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Hematology blood test (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: D-Dimer test (coagulation) (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Inflammatory markers (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Vital signs (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: VAS scale (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: WHO Ordinal Score (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: COVID-19-Related Symptoms assessment (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: COVID-19-Impact on Quality-of-Life Questionnaire (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Pregnancy test (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Physical examination (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: PK parameters (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: SARS-CoV-2 test (PCR) (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: ECG (Diagnostic Test)
Arm 2 - CimetrA-2
CimetrA-2, with a total dose containing a combination of Curcumin 28 mg, Boswellia 21 mg and Vitamin C 84 mg in spray administration - divided in 4 separate doses given as an add on therapy, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Treatment administration (twice a day) (Drug)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Biochemistry blood test (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Hematology blood test (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: D-Dimer test (coagulation) (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Inflammatory markers (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Vital signs (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: VAS scale (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: WHO Ordinal Score (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: COVID-19-Related Symptoms assessment (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: COVID-19-Impact on Quality-of-Life Questionnaire (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Pregnancy test (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Physical examination (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: PK parameters (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: SARS-CoV-2 test (PCR) (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: ECG (Diagnostic Test)
Arm 3 - Placebo
Placebo, composed of the same solvent but without active ingredients, given as an add on therapy in spray administration, total of 4 doses over 48 hours (day 1 and day 2), twice a day (morning and evening).
干预措施: Treatment administration (twice a day) (Drug)
结局指标
主要结局
Change in WHO Ordinal Scale for clinical improvement
时间窗: up to 28 days
measured on days 1, 7, 14, 28 numerical value to assess the health status of the participant , scale is between 0-8 , The higher score means the worse outcome .
Change in COVID-19-Related Symptoms score
时间窗: up to 28 days
measured on days 1,7, 14, 28 numerical value to assess the COVID-19-Related symptoms of participant scale is between 0-3, The higher score means the worse outcome . score 0-3; higher score indicates worse outcome.
Safety endpoint: will be assessed through collection and analysis of adverse events
时间窗: up to 28 days
Data management team will assess and review the AE's and SAE'S.
Safety endpoint: will be assessed through collection and analysis of blood laboratory test.
时间窗: up to 28 days
Data management team will assess and review the lab test results (blood), assessment will be compared to the normal range. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition
Safety endpoint: will be assessed through collection and analysis of urine laboratory test.
时间窗: up to 28 days
Data management team will assess and review the lab test results (urine), assessment will be compared to the normal range. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition
Safety endpoint: will be assessed through collection and analysis of blood preasure
时间窗: up to 28 days
units: BPM (beats per minute) Data management team will assess and review the vital signs : blood pressure \[mm Hg\], saturation \[%\], body temperature \[C\] , Each category of the assessments will be compared to the normal ranges. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition
Safety endpoint: will be assessed through collection and analysis of blood satturation
时间窗: up to 28 days
units: %O2 Data management team will assess and review the vital signs : blood pressure \[mm Hg\], saturation \[%\], body temperature \[C\] , Each category of the assessments will be compared to the normal ranges. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition
Safety endpoint: will be assessed through collection and analysis of body temperature
时间窗: up to 28 days
units: celsius degrees Data management team will assess and review the vital signs : blood pressure \[mm Hg\], saturation \[%\], body temperature \[C\] , Each category of the assessments will be compared to the normal ranges. Exceptional values above the norm or below the norm indicate an aggravation of the participant's condition
次要结局
- duration of mechanical ventilation(up to 28 days)
- Incidence of Intensive Care Unit (ICU) stay during COVID-19 complication(up to 28 days)
- Percentage of participants with definite or probable drug related adverse events(up to 28 days)
- Number of participants with depending on oxygen supplementation through day 28 since onset of symptoms(up to 28 days)
- Long term adverse events of COVID-19 on Day 28(up to 28 days)
- Change in inflammatory marker levels - IL-6, IL-1β, IL-12, TNF α, IFN-γ, CRP, NLR (Neutrophil / Lymphocyte ratio) at days 1, 2, 4, 7, compared to baseline(up to 7 days)
- Pharmacokinetic profile of the study drug(on day 1 through 24 Hrs)
- Pharmacokinetic profile of the study drug - maximal concentartion(on day 1 through 24 Hrs)
- Pharmacokinetic profile of the study drug - elimination rate constant (denoted as K)(on day 1 through 24 Hrs)
- Pharmacokinetic profile of the study drug - half-life(on day 1 through 24 Hrs)
- Pharmacokinetic profile of the study drug - apparent volume of distribution(on day 1 through 24 Hrs)
- Pharmacokinetic profile of the study drug - total clearance rate(on day 1 through 24 Hrs)
- Pharmacokinetic profile of the study drug - AUC(on day 1 through 24 Hrs)
- The Impact covid_19 on Quality of life of patients on Days 1, 14 and 28.(up to 28 days)
- Course of change in D Dimer levels compared to baseline(up to 28 days)
- Occurrence of secondary infections(up to 28 days)
- Incidence of mechanical ventilation(up to 28 days)