Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory Therapy in Patients Diagnosed With COVID-19 Disease
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 516
- 试验地点
- 4
- 主要终点
- Rate of disease remission.
研究概览
简要总结
The aim of the study is to clinically use bovine Lf as a safe antiviral adjuvant for treatment and to assess the potential in reducing mortality and morbidity rates in COVID-19 patients. The study was approved by the ethical committee of the Egyptian Center for Research and Regenerative Medicine in 11-5-2020.
详细描述
The World Health Organization (WHO) declared the coronavirus (SARS-CoV-2, COVID-19) outbreak a Public Health Emergency of International Concern with a pandemic spread. The situation is rapidly evolving, which raises the approach of reproposing already approved drugs to meet the emerging challenge and to save time and money. Lactoferrin (Lf) is a natural glycoprotein that broadly distributed within the body fluids and found predominantly in milk. It represents a known component of the innate immune system. The antiviral activity of Lf has been reported against many viruses, including SARS-CoV-1, through blocking the viral receptors on the host cells preventing them from entry and replication. Markedly, data reveals that Lf interacts with Heparan Sulfate Proteoglycans (HSPGs) and Angiotensin Converting Enzyme 2 (ACE2) receptors that are reported as SARS-CoV-2-binding sites to enter the host cell, suggesting a potential significance of Lf as an antiviral against SARS-CoV-2. Moreover, the immunoregulatory effects of Lf can protect against the cytokine-storm and thrombotic complications that result from the COVID-19-induced over-stimulated inflammatory response and exaggerated immune reactions. In addition, Lf can decrease the free iron toxicity caused by the virus as it has a strong iron chelating ability. Lf is a safe approved food supplement that is available in the markets for enhancement of immunity and for treatment of anemia. The aim of this study is to perform a randomized, double-blind, placebo-controlled, two arms, clinical trial to assess oral enteric-coated tablet of bovine apolactoferrin (the low iron-content form of Lf) as a safe antiviral and immunoregulatory therapy in patients diagnosed with COVID-19 disease.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients tested positive (PCR) for SARS-CoV-2 and clinically symptomatic.
- •Adult patients with age >18 years.
- •Patients willing and able to sign the study informed consent form.
排除标准
- •Critically severe disease patients (having Respiratory failure requiring mechanical ventilation, or signs of septic shock or multiple organ failure requiring ICU admission).
- •Patients who are unconscious
- •Patients who have convulsions
- •Patients suffering from central cyanosis with SPO2< 90% (for asthmatic patients with SPO2<88%)
- •Pregnant or lactating women
- •Patients with a known history of pro-inflammatory diseases (patients with autoimmune diseases, patients receiving chemotherapy for cancer, patients with malabsorption, patients with inflammatory bowel disease, Crohn's disease or ulcerative colitis).
- •History or suspected immunosuppressive or immunodeficient state including HIV infection, or chronic immunosuppressant medication (more than 14 days) within the past 3 months (inhaled and topical steroids are allowed).
- •Patients with severe renal impairment (GFR <60 ml/min/1.73m2 as measured by the Cockcroft-Gault formula).
- •Patient with severe hepatic impairment, biliary cirrhosis or cholestasis
- •Patients who received immunoregulatory therapy within one month before the start of the study.
- •Patients with Known or suspected allergy or any contraindications to Lactoferrin.
- •Any condition, according to the judgment of the investigator, would interfere with the patient's ability to comply with all study requirements or that would place the patient at unacceptable risk by his/her participation in the study.
研究组 & 干预措施
Arm 01 (SOC + Lactoferrin 1200 mg QID)
Patients randomized to this group will receive two 600 mg Lactoferrin tablets QID plus the Standard of Care (SOC) treatment(s).
干预措施: Lactoferrin (Apolactoferrin) (Dietary Supplement)
Arm 02 (SOC + Placebo QID)
Patients randomized to this group will receive two placebo tablets QID plus the SOC treatment(s).
干预措施: Placebo of excipient(s) will be administered (Drug)
结局指标
主要结局
Rate of disease remission.
时间窗: up to 4 weeks.
For mild/moderate symptoms patients: fever, cough and other symptoms relieved with improved lung CT - For severe symptoms patients: fever, cough and other symptoms relieved with improved lung CT, and oxygen saturation by pulse oximetry (SPO2 )\> 93% for nonasthmatic patients, and from 88-92% in asthmatic patients.
The number of patients with PCR negative results.
时间窗: up to 4 weeks.
Comparing the influence of the intervention on the PCR negative results.
Survival rate.
时间窗: up to 8 weeks.
Comparing the influence of the intervention on the Survival rate.
次要结局
- Mean change in blood pressure.(up to 4 weeks.)
- Mean change in oxygen saturation.(up to 4 weeks.)
- Mean change in liver Albumin.(up to 4 weeks.)
- Mean change in prothrombin time (PT) and partial thromboplastin time (PTT ).(up to 4 weeks.)
- Mean changes in immunoglobulin G (IgG).(up to 4 weeks.)
- Mean change in the disease severity (clinical assessment).(up to 4 weeks.)
- Mean change in the ratio in arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).(up to 4 weeks.)
- Mean change in Serum Creatinine.(up to 4 weeks.)
- Mean change in complete blood picture (CBC).(up to 4 weeks.)
- Mean change in total and direct Bilirubin.(up to 4 weeks.)
- Mean change in Alanine Aminotransferase (ALT).(up to 4 weeks.)
- The mean change in serum interleukin-10 (IL-10).(up to 4 weeks.)
- The mean change in serum tumor necrosis factor-alpha (TNF alpha).(up to 4 weeks.)
- Mean change in body temperature.(up to 4 weeks.)
- Mean change in body respiratory rate.(up to 4 weeks.)
- Mean change in ferritin.(up to 4 weeks.)
- Mean change in aspartate aminotransferase (AST).(up to 4 weeks.)
- Mean change in Blood Urea Nitrogen (BUN).(up to 4 weeks.)
- Mean change in Serum Creatinine clearance.(up to 4 weeks.)
- Mean change in heart beats.(up to 4 weeks.)
- Mean change in C reactive protein (CRP).(up to 4 weeks.)
- Mean change in erythrocyte sedimentation rate (ESR).(up to 4 weeks.)
- Mean change in D-dimer.(up to 4 weeks.)
- Mean change in Glomerular filtration rate (GFR ).(up to 4 weeks.)
- The mean change in serum interleukin-6 (IL-6).(up to 4 weeks.)
- Mean changes in immunoglobulin M (IgM).(up to 4 weeks.)
- The mean change in PCR viral load.(up to 4 weeks.)
- Mean change in lung CT manifestation.(up to 4 weeks.)
- The mean change in serum interleukin-1 (IL-1).(up to 4 weeks.)
- Nature and severity of Adverse Events.(up to 4 weeks.)
- The number of missed drug doses among each treatment group.(up to 4 weeks.)
- Time for lung recovery.(up to 8 weeks.)
研究者
Rehab Ragab Hegazy
Assistant Professor
National Research Centre, Egypt