Clinical trial NCT04407130: Efficacy and Safety of Ivermectin and Doxycycline in Combination or IVE Alone in Patients With COVID-19 Infection.
Official title: Ivermectin and Doxycycline in Combination or Ivermectin Alone for the Treatment of Adult Bangladeshi Patients Hospitalized for COVID-19: a Randomised, Double-blind, Placebo-controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19 Patients
Lead sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh
Sponsor class: OTHER
First posted: 2020-05-29
Enrollment: 72
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled Trial
Primary purpose: TREATMENT

Brief summary: Burden:

Initial outbreak of corona virus disease 2019 (COVID-19) was reported from Wuhan, China in early December 2019.Presently known to be caused by a novel beta-corona virus, named as Severe acute respiratory syndrome corona virus 2 ( SARS-CoV-2).

World Health Organization (WHO) declared a pandemic on March.

The clinical characteristics of COVID-19 include respiratory symptoms, fever, cough, dyspnoea and pneumonia

Infected individuals exhibit:

1. Mostly mild illness (80% +) recover without any treatment (\~80%)
2. Moderate illness that needs hospitalization and recovers after standard
3. supportive treatment (\~14%)
4. Critical illness (\~5%) needs ICU support
5. Death (1-2% )

COVID-19 has now spread \>210 countries and territories globally. SARS-CoV-2 is a respiratory virus which spreads primarily through droplets generalized when an infected person coughs or sneezes or through droplets of saliva or discharge from the nose.

Symptomatic management remains the mainstay of treatment strategy. Mortality appears to be more common in older individuals and those with co-morbidities, such as chronic lung disease, cardiovascular disease and diabetes. Young people with no comorbidities also appear to be at risk for critical illness including multi-organ failure and death. Seen more in Bangladesh between 21-40 yrs of age.

Knowledge Gap:

There is no specific treatment against this new virus that WHO has officially declared until now.There are many pharmacologic therapies that are being used or considered for treatment of COVID-19. National Guidelines on Clinical Management of Corona virus Disease 2019 (Covid-19): V 5.0 date 9th April 2020) CDC, DGHS, GoB

Thus an RCT is urgently needed in Bangladesh: Based on recent literatures on Rx studies in COVID-19 patients from other countries as well as its availability \& affordability of those repurposed medicines

Detailed description: Objectives:

General Objective:

The aim of the study is to evaluate efficacy and safety of ivermectin in combination with doxycycline or ivermectin alone for the treatment of hospitalized SARS-CoV-2 infected adult Bangladeshi COVID-19 +ve patients and to compare with placebo; where all three arms will receive the standard care of treatment of COVID-19 infected patients in the hospital. By successful demonstration of the safety and efficacy of these repurposed medicines, it may have the potential to play an important role in the treatment of COVID-19+ve patients.

Specific Objective:

1. Duration of the virological clearance rate
2. Days required for remission of fever and cough

Secondary Objective:

* Patients requiring oxygen
* Patients failing to maintain SpO2 \>88 despite oxygenation
* Number of days on oxygen support
* Chest X-ray improvement
* Duration of hospitalization
* All cause mortality

Eligibility criteria: Inclusion criterion:

* Bangladeshi aged 18-65 years admitted to any of the aforementioned study sites (hospitals)
* Either sex
* At the enrollment having at least one of the following symptoms: Temp 37.5 C or above, Cough, Sore throat
* SpO2 \>94%
* Duration of illness ≤ 7 days
* No oxygen support on enrollment
* Capable of swallowing oral medication
* PCR positive for SARS-CoV2 virus
* The participant properly informed about the study and agreed to sign the informed consent form (ICF)

Exclusion Criteria:

* Allergy to ivermectin or doxycycline; or other contraindications to any of the study medications
* History of chronic heart disease (IHD, heart failure, documented cardiomyopathy etc)
* History of chronic liver disease (SGPT value more than 3 times of normal value)
* History of chronic kidney disease (S. Creatinine for male \>1.3 mg/dL or \>115 µmol/L and for female \>1.2 mg/dL or \>106.1 µmol/L)
* Pregnant or lactating women
* Participated in any other clinical trial within last 4 weeks
* H/o received Ivermectin/Doxycycline within last 7 days

Primary outcomes:
measure: Virological clearance
timeFrame: within 7 days after enrollment
measure: Remission of fever
timeFrame: within 7 days after enrollment
measure: Remission of cough
timeFrame: within 7 days after enrollment
Secondary outcomes:
measure: Patients requiring oxygen
timeFrame: within 7 days after enrollment
measure: Patients failing to maintain SpO2 >93% despite oxygenation
timeFrame: within 7 days after enrollment
measure: Number of days on oxygen support
timeFrame: within 7 days after enrollment
measure: Duration of hospitalization
timeFrame: within 14 days after enrollment
measure: All causes of mortality
timeFrame: within 14 days after enrollment
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Icddr,B
Study officials:
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Wasif Ali Khan, MBBS, MHS
role: PRINCIPAL_INVESTIGATOR
References: