The Role of High Dose Co-trimoxazole in Severe Covid-19 Patients

• Status: Not yet recruiting
• Trial end date: 2021-11-14
• Target enrollment: 0
• Participant gender: All

Summary

Coronavirus Disease 19 (COVID-19) is a worldwide pandemic and a major global health concern which is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The newly emerged Coronavirus disease 2019 (COVID-19), which was first identified in Wuhan, China, has swept through 219 countries, killing a staggering number of people. According to WHO reports, the number of deaths had risen to 3,155,168by March 30, 2021, out of 149,910,744 confirmed cases. In Bangladesh, the outbreak has infected over 745,322confirmed cases, with over 11,053 deaths reported. Though the patient may be asymptomatic or present with mild symptoms, mortality is quite high in the severe form of the disease which often progresses to critical phase presented as Acute Respiratory Distress Syndrome (ARDS). This is due to exaggerated response of immune system to the virus termed as cytokine storm syndrome (CSS). There is currently no effective antiviral therapy for SARS-CoV-2 and supportive care is the mainstay of therapy. As a result we are still searching for a better therapeutic agent which will help in treating Covid-19 cases in terms of mortality, morbidity, oxygen requirement, length of stay in hospital. Co-trimoxazole (composed of one-part Trimethoprim and five parts Sulfamethoxazole)is a sulphur containing anti-folate bactericidal drug which is being used for over 60 years for various indications esp. respiratory tract infections. It is known to have immunomodulatory and anti-inflammatory properties that may help to prevent progression to critical phase and cytokine storm syndrome in severe COVID-19 patients. It acts rapidly when given in high dose due to its better bioavailability and lung penetration. Low cost and a good safety profile can make it an ideal candidate for treatment of COVID -19 in a low resource country like Bangladesh.

Methods and materials:

This interventional double-blind place controlled randomized trial will be conducted in the department of medicine at Bangabandhu Sheikh Mujib Medical University (BSMMU) 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 high dose co-trimoxazole in addition to standard therapy or placebo along with standard therapy. 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 28- day mortality between the two groups will be compared. Data will be collected from case record forms, anonymised and stored securely in a secure online web based portal. Statistical analysis will be performed using t-test or Mann -Whitney U test or Wilcoxon signed rank test for continuous variables and Chi- square test or Fisher's exact test for categorical variables. Survival will be assessed by the Kaplan-Meier method. Comparisons between two groups will be performed using the log-rank test. A p-value of < 0.05 will be considered to be significant. The statistical software SPSS version 25 will be used for the analysis.

Conclusion If the results from this clinical trial demonstrate the beneficial effects of high co-trimoxazole in patients with severe COVID-19 it could help to reduce the need for respiratory support for thousands of patients, saving valuable lives and decrease the burden of healthcare system in countries with limited resources.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
• Treatments: Trimethoprim, Sulfamethoxazole Drug Combination

Criteria

Inclusion criteria

• Confirmed COVID-19 patients by RT-PCR

• Clinically suspected COVID-19 patients

• Age > 18 years

• Patients requiring oxygen at least> 5L/min up to 15 L/min (by FM/ NRM)to maintain saturation >92% to 96%

NOTE: Clinically suspected COVID-19 = fever (Temperature >37.8 Degree Celsius) + respiratory symptoms + Radiological evidences Exclusion criteria

• Multi-organ failure

• Severe ARDS (requiring HFNC orventilatory support on presentation in the form ofinvasive or non-invasive ventilation)

• Septic Shock

• Severe liver disease

• Acute Heart Failure

• Acute Kidney Injury (where GFR< 15 and plasma-sulfamethoxazoleconcentration cannot be monitored)

• Drug allergy/intolerance to co-trimoxazole / Sulphar sensitivity

• Pregnancy