JOURNAL ARTICLE

Role of Co-trimoxazole in Severe COVID-19 Patients

NHS Libraries-NCT04470531 undefined.
Role of Co-trimoxazole in Severe COVID-19 Patients (2020)

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 [alpha] (TNF [alpha]) 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, Specific Objectives:, To assess length of
stay who are treated with co-trimoxazole in addition to standard treatment versus standard
treatment alone., To find out side effects (rash.itching. dizziness, headache, nausea,vomiting,
diarrhea, sore throat, unusual bruising or bleeding, yellowing of the skin or eye discolorations, joint
or muscle pain,red or purple skin.etc) of drugs who are treated with co-trimoxazole in addition to
standard treatment versus standard treatment alone., To find out requirement for ventilator support
(non-invasive and invasive ventilation) who are treated with co-trimoxazole in addition to standard
treatment versus standard treatment alone., To assess the mortality in patients with severe COVID-
19 who are treated with co-trimoxazole in addition to standard treatment versus standard
treatment alone., Study design:Open-label randomized controlled trial Study duration: Six months.,
Study Population:, Patients presenting to participating hospitals in Bangladesh with symptoms
ofCOVID-19 will be assessed for eligibility., Inclusion criteria, 1. Diagnosed COVID-19 patients ( RT-
PCR positive for COVID-19), 2. Age > 18 years, 3. Hypoxic respiratory failure (saturation <90% on air
at rest or increasing oxygen requirement), 4. Chest examination findings of bilateral crackles on
auscultation or chest x-ray showing bilateral infiltrates, 5. C-Reactive Protein > 50mg/L, Exclusion
criteria, 1. Multi-organ failure, 2. Severe ARDS (requiring ventilator support on presentation in the
form of invasive or non-invasive ventilation), 3. Septic Shock, 4. Severe liver disease, 5. Acute
Kidney Injury (where GFR< 15 and plasma-sulfamethoxazoleconcentration cannot be monitored),
6. Drug allergy/intolerance to co-trimoxazole / Sulphar sensitivity, 7. Pregnancy, 8. Already receiving
Tocilizumab or convalescent therapy Sampling procedure:This RCT will consist of two arms,
experimental group and control group.Randomized (1:1) case: control, (non-blinded) trial. 1.
control group will receive standard treatment, 2. experimental group will recivestandard care and
oral co-triamoxazole. Forty-seven (47) patients will be enrolled for each arm. Randomization
will be done by a random number table. Allocations will be in sequentially numbered.,
Treatment protocol Eligible patients will be received either to oral co-trimoxazole + standard therapy
or standard therapy alone. (According to institution /national protocol), The following treatments
are recommended as standard therapy:, 1. Antibiotics for secondary bacterial infection as per
institutional guidelines, 2. Supplemental oxygen (to keep saturations between 90% to 96%), 3.
Intravenous hydration (to maintain euvolumia), 4. Thrombo-prophylaxis as per local guidelines, 5.
Paracetamol (oral or I/V 1gram QDS as required or regular), 6. To consider steroids if indicated (i.e.
acute exacerbation of COPD or acute severe asthma) NOTE: The dose of co-trimoxazoleis 960 mg
(trimethoprim 160mg + sulphamethoxazole 800mg) twice daily for 7 days orally., sample size: 94,
Research instrument:, 1. General questionnaire for assessing socio-demographic data., 2. A checklist
of clinical findings, 3. A checklist of investigation findings., Measures Variable:, Data collection
required for both groups (co-trimoxazole + standard therapyand standard therapy alone), 1. Age, 2.
Sex, 3. Ethnicity, 4. Past medical history - Hypertension, use of ACEI or ARB, DM, IHD, COPD, CKD,
Obesity (BMI) andCancer, 5. Presenting symptoms (dry cough, productive cough, fever, sore
throat, myalgia, lethargy, headache, breathlessness, nausea, diarrhoea and any other), 6. Baseline
observations on dayof initiating treatment (Day 0): oxygen saturation(SpO2), fraction of inspired
oxygen (FiO2) , SpO2/FiO2 ratio, respiratory rate, body temperature, neutrophil-lymphocyte ratio,
C-Reactive Protein&findings of bilateral infiltrates on chest-x-ray., 7. Follow-up observations after
randomization on Day 1,2,3,4 and 5 for SpO2/FiO2 ratio, respiratory rate,body temperature and
C-Reactive Protein, 8. Length of stay (in days), 9. Use of ventilator support (invasive or non-invasive
ventilation), 10. Side effects of drugs, 11. In-patient mortality Primary end points, 1. Length of stay in
hospital (in days) 2. In-patient mortality, Secondary end points, 1. Change in observations after
randomization on Day 1,2,3,4 and 5 for SpO2/FiO2 ratio, respiratory rate, body temperature and
C-Reactive Protein, 2. Use of ventilator support (invasive or non-invasive ventilation), 3. Side effects
of drugs co-trimoxazole, Data Collection procedure:, Pre-designed case record form (CRF) will be
used for collecting data, which will also contain the result of the study. The information collected in
the CRF will be reviewed and inconsistencies will be investigated and clarified. Data from case record
forms will be anonymised and stored securely in a secure online web-based portal., Statistical
analysis: 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 and Hazard regression 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.