Role of Co-trimoxazole in Severe COVID-19 Patients
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- In-patient mortality
研究概览
简要总结
Coronavirus Disease 19 (COVID-19) is a global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Severe disease occurs in 15% of the cases with COVID-19 and may progress to critical disease in only 5% of the cases with a high risk of mortality. Critical disease may present as acute respiratory failure secondary to Acute Respiratory Distress Syndrome (ARDS) and is caused by the body's hyper-immune response to the virus in the form of a cytokine storm syndrome (CSS). There is currently no effective anti-viral treatment against SARS-CoV-2 and the mainstay of treatment is supportive. Co-trimoxazole (combination of trimethoprim and sulphamethoxazole in a 1:5) ratio is a Sulphur containing anti-folate bactericidal antibiotic indicated for the treatment of respiratory tract infections. It has been around for over 60 years and is inexpensive and readily available with a good safety profile. It has a rapid onset of action with excellent bioavailability and lung penetration. In addition to having antimicrobial properties co-trimoxazole have immunomodulatory and anti-inflammatory properties and may be a potential treatment option for cytokine storm syndrome mediated severe COVID-19.
This open-label randomized controlled trial will be conducted in the department of medicine at Bangabandhu Sheikh Mujib Medical University (BSMMU), Anwar Khan Modern Medical college and Mughda Medical College Hospital (DMCH), Dhaka for a duration of 6 months following approval of this protocol. It will recruit at least 94 consecutive adults (18 years or older) patients with clinically suspected COVID-19 and severe illness as per WHO criteria. After taking informed written consent patients will be randomly assigned in a 1:1 ratio to either oral co-trimoxazole in addition to standard therapy or standard therapy alone. Baseline characteristics, changes in the physiological and biochemical parameters like (SpO2/FiO2 ratio, respiratory rate, body temperature and C - reactive protein), length of hospital stay, side effects of drugs, requirement for ventilatory support (non-invasive and invasive ventilation) and in-patient mortality between the two groups will be compared.
Conclusion If the results from this clinical trial demonstrate the beneficial effects of co-trimoxazole in severe COVID-19 patients it could be used widely, thereby reducing the need for respiratory support and potentially saving thousands of lives in developing nations with limited resources where healthcare may be easily overwhelmed.
详细描述
Coronavirus disease (COVID-19) caused by SARS-COV2, represents a highly transmissible and potentially fatal disease that is of great global public health concern at this moment. The pandemic situation in Bangladesh is also evolving rapidly with positive cases and deaths increasing each day. Epidemiological changes in COVID-19 infection should be monitored taking into account potential routes of transmission and subclinical infections, in addition to the adaptation, evolution, and virus spread among humans and possible intermediate animals and reservoirs. But till today there is no specific management to deal with this highly deadly viral infection. Howeverthere are few drugs which might cause some beneficial effects in the recovery of the patient. Cotrimoxazole is a time tested antibiotic which has been in clinical use for 60 years with anti-bacterial action against a wide range of organism. In addition to the antimicrobial effects, co-trimoxazole has anti-inflammatory and immunomodulatory effects. Co-trimoxazole has previously been shown to exert anti-cytokine effect by inhibiting interleukin 1, 6 (IL-1, IL-6) and Tumour Necrosis Factor α (TNF α) which are the major cytokines identified in patients with severe COVID-19. As in some case reports this has shown significant clinical improvement in ARDS, so there is a possibility, that cotrimoxazole might have also role in improving the clinical outcome in COVID-19 patients especially in moderate to severe cases. As till today there is no specific treatment for COVID-19 infections, if cotrimoxazole ifs found to be effective this will bring a great benefit to the target populations. Beside this, cotrimoxazole is a very cheap drug in comparison to other ones this will also be of great economical benefit in taking cares of the general population. As there is no such study published about the role of cotrimoxazole in COVID-19 patients, this study will generate a new information which bring a great benefit in battling with the COVID-19 infection.
Research Question:
What is the outcome of co-trimoxazole in severe COVID-19 patients?
Objectives:
General Objectives To assess the clinical outcome of co-trimoxazolein patients with severe 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
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed COVID-19 patients ( RT-PCR positive for COVID-19)
- •Age > 18 years
- •Hypoxic respiratory failure (saturation <90% on air at rest or increasing oxygen requirement)
- •Chest examination findings of bilateral crackles on auscultation or chest x-ray showing bilateral infiltrates
- •C-Reactive Protein > 50mg/L
排除标准
- •Multi-organ failure
- •Severe ARDS (requiring ventilator support on presentation in the form of invasive or non-invasive ventilation)
- •Septic Shock
- •Severe liver disease
- •Acute Kidney Injury (where GFR< 15 and plasma-sulfamethoxazoleconcentration cannot be monitored)
- •Drug allergy/intolerance to co-trimoxazole / Sulphar sensitivity
- •Already receiving Tocilizumab or convalescent therapy
研究组 & 干预措施
intervention /experimental
Arm B: Experimental Arm received oral co-trimoxazole + standard therapy
The following treatments are recommended as standard therapy:
- Antibiotics for secondary bacterial infection as per institutional guidelines
- Supplemental oxygen (to keep saturations between 90% to 96%)
- Intravenous hydration (to maintain euvolumia)
- Thrombo-prophylaxis as per local guidelines
- Paracetamol (oral or I/V 1gram QDS as required or regular)
- To consider steroids if indicated (i.e. acute exacerbation of COPD or acute severe asthma)
干预措施: oral co-trimoxazole (Drug)
结局指标
主要结局
In-patient mortality
时间窗: 14 days
% of patients died after enrollment
Length of stay in hospital (in days)
时间窗: 14 days
Duration of hospital stay in days
次要结局
- respiratory rate(Day 1,2,3,4 and 5)
- C-reactive Protein(Day 1,2,3,4 and 5)
- Fever(Day 1,2,3,4 and 5)
- SpO2/FiO2 ratio(Day 1,2,3,4 and 5)
- Ventilator support(14 days)
- Proportion of drug adverse reaction(24 hours)
研究者
Prof. Dr. Shohael Mahmud Arafat
Chairman and professor of internal medicine
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh