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

NCT04884490 | Completed Phase 2 DMC

• 1 other identifier: BSMMU/2021/4098(A)
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

COVID-19 Pneumonia

Keywords

COVID-19, Co-trimoxazole, RCT

Outcome Measures

Primary Outcomes (1)

• Length of stay in hospital (in days)

  How long the patient needs hospital care

  Upto 28 days

Secondary Outcomes (8)

• Change in observations after randomization on Day 3 and 7

  Day 3, Day 7

• Change in observations after randomization on Day 3 and 7

  Day 3, Day 7

• Change in observations after randomization on Day 3 and 7

  Day 3, Day 7

• Use of High Flow

  Day 28

• ITU requirement

  Day 28

Study Arms (2)

Intervention

EXPERIMENTAL

Eligible patients will be receiving either to oral co-trimoxazole + standard therapy. Tab. Co-trimoxazole 960 mg (trimethoprim 160mg + sulphamethoxazole 800mg) thrice (8 hourly) daily for 7 days orally. 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 92% 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 in appropriate cases. 7. Nasopharyngeal and throat swab to be sent for RT PCR to detect SARS-CoV-2 (if not already done) and blood culture Tab. Co-trimoxazole 960 mg (trimethoprim 160mg + sulphamethoxazole 800mg) thrice (8 hourly) daily for 7 days orally.

Drug: Co-trimoxazole

Standard

PLACEBO COMPARATOR

Standard therapy along with placebo. Placebo thrice (8 hourly) for 7 days. 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 92% 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 in appropriate cases. 7. Nasopharyngeal and throat swab to be sent for RT PCR to detect SARS-CoV-2 (if not already done) and blood culture

Drug: Placebo

Interventions

Co-trimoxazole DRUG

Tab. Co-trimoxazole 960 mg (trimethoprim 160mg + sulphamethoxazole 800mg) thrice (8 hourly) daily for 7 days orally.

Intervention

Placebo DRUG

Placebo thrice (8 hourly) daily for 7 days orally.

Standard

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh: lead

Study Sites (1)

Bangabandhu Sheikh Mujib Medical University

Dhaka, 1200, Bangladesh

Location

MeSH Terms

Conditions

COVID-19

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: A data sheet (enclosed) will be prepared, for which a short interview of less than 30 minutes will be required. Ethical risks are deemed minimal as standard therapy as well as co-trimoxazole are extensively used treatments and have well-documented efficacy\& safety. Placebo will be used here along with standard therapy in the control group. Informed oral and written consent will be taken from the study subjects. Patient will be given packs containing total number of 27 tablets of Co-trimoxazoles or placebo which will be coded by a personnel not involved in the study. Research assistant and investigators will not be aware of the drug. After data collection and entry during analysis decoding will be done.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor of Internal Medicine

Model Details: Study design:Single-centre interventional Prospective double-blind placebo controlled randomized trial. Study duration: Six months. Place of study: Medicine department (Covid Unit) of Bangabandhu Sheikh Mujib Medical University (BSMMU) Period of Study: Six months following approval of the protocol Sampling technique: Random sampling followed by patients will be assigned in a 1:1 ratio to either oral high dose co-trimoxazole in addition to standard therapy or standard therapy along with placebo Sample Size: 47 in each group

Study Record Dates

• First Submitted: May 5, 2021
• First Posted: May 13, 2021
• Study Start: May 15, 2021
• Primary Completion: October 14, 2021
• Study Completion: November 14, 2021
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)