Efficacy and Safety of Ivermectin and Doxycycline in Combination or IVE Alone in Patients With COVID-19 Infection.

• ClinicalTrials.gov Identifier: NCT04407130
• Recruitment Status: Completed
• First Posted: May 29, 2020
• Last Update Posted: February 4, 2021
• Sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh
• Information provided by (Responsible Party): International Centre for Diarrhoeal Disease Research, Bangladesh

Study Description

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

Condition or disease	Intervention/treatment	Phase
COVID-19 Patients	Drug: Ivermectin + Doxycycline + Placebo; Drug: Ivermectin + Placebo; Drug: Placebo	Phase 2

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, Double-Blind, Placebo-Controlled Trial
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: June 16, 2020
• Actual Primary Completion Date: October 30, 2020
• Actual Study Completion Date: November 20, 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Tab Ivermectin +Cap Doxycycline; 200 mcg/kg (12 mg tablet) ivermectin (IVERA) single dose and 200 mg stat doxycycline day-1 followed by 100mg doxycycline 12hrly for 4 day (i.e. day2-day5) + Placebo one tablet D2-5	Drug: Ivermectin + Doxycycline + Placebo; Arm I: 200 mcg/kg (12 mg tablet) ivermectin (IVERA) single dose and 200 mg stat doxycycline day-1 followed by 100mg doxycycline 12hrly for 4 day (i.e. day2-day5) Placebo one tablet D2-5; Other Name: Tab IVERA +Cap Doxycycline
Active Comparator: Tab Ivermectin; Ivermectin - 200 mcg/kg (12 mg tablet) once per day D1-D5 + Placebo two tablets D1 followed by Placebo one tablet D2-5	Drug: Ivermectin + Placebo; Arm II: Ivermectin - 200 mcg/kg (12 mg tablet) once per day D1-D5 + Placebo two tablets D1 followed by Placebo one tablet D2-5; Other Name: Tab IVERA
Placebo Comparator: Placebo; Drug: Placebo 3 Placebo tablets D1 followed by 2 tablets D2-5	Drug: Placebo; Arm III: 3 Placebo tablets D1 followed by 2 tablets D2-5; Other Name: Tab Placebo

Outcome Measures

Primary Outcome Measures :

1. Virological clearance [ Time Frame: within 7 days after enrollment ]
   • Presence of virus will be negative on Day 7 detected by RT PCR
2. Remission of fever [ Time Frame: within 7 days after enrollment ]
   • Body temperature will be < 37.5 C by day 7 detected by Infrared thermometer
3. Remission of cough [ Time Frame: within 7 days after enrollment ]
   • Remission of cough: No signs of cough showing respiratory rate within 12-20/ min, on day7

Secondary Outcome Measures :

1. Patients requiring oxygen [ Time Frame: within 7 days after enrollment ]
   Detected SPO2 level <94% on Day 7or before by pulse oxymeter
2. Patients failing to maintain SpO2 >93% despite oxygenation [ Time Frame: within 7 days after enrollment ]
   Patients who fail to maintain pulse oxymeter detected SpO2 level>93% despite O2 supplementation of 2-6 L/min, on Day 7 or before
3. Number of days on oxygen support [ Time Frame: within 7 days after enrollment ]
   Any number of days on oxygen support on Day 7 or before recorded in CRF
4. Duration of hospitalization [ Time Frame: within 14 days after enrollment ]
   Hospital stay ≥7days to ≤14 days as per CRF records
5. All causes of mortality [ Time Frame: within 14 days after enrollment ]
   Death any time during 14 days of study period from any cause recorded in CRF and Hospital death certificate

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Bangladesh

Icddr,B

Dhaka, Bangladesh, 1000

Sponsors and Collaborators

International Centre for Diarrhoeal Disease Research, Bangladesh

Investigators

• Principal Investigator: Wasif Ali Khan, MBBS, MHS; International Centre for Diarrhoeal Disease Research, Bangladesh

More Information

• Responsible Party: International Centre for Diarrhoeal Disease Research, Bangladesh
• ClinicalTrials.gov Identifier: NCT04407130
• Other Study ID Numbers: PR-20039
• First Posted: May 29, 2020
• Last Update Posted: February 4, 2021
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Doxycycline; Ivermectin; Anti-Bacterial Agents; Anti-Infective Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents