Clinical Trial of Ivermectin Plus Doxycycline for the Treatment of Confirmed Covid-19 Infection

NCT04523831 | Completed Phase 3 Results DMC

• 1 other identifier: ERC-DMC/ECC/2020/117
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

On 31 December 2019, the World Health Organization (WHO) was formally notified about a cluster of cases of pneumonia in Wuhan City, China. On 7 January the responsible virus was isolated and its genome sequence was shared on 12 January. It was named as COVID-19, a novel Coronavirus, SARS-CoV-2. It is a member of the Corona virus family which is RNA enveloped viruses. Very rapidly the virus emerged as pandemic. Now it is dominating the lives of every people of this universe. Management of the COVID-19 relies on mainly supportive care and oxygen supplementation via non-invasive or mechanical ventilation in critical cases. Patients who are critically ill may also require vasopressor support and antibiotics for secondary bacterial infections. There is no vaccine or highly effective antiviral drugs for COVID-19. Currently there is a tremendous effort around the world to develop effective preventive and therapeutic treatment for this disease. World Health Organization has launched a non-blinded clinical trial (SOLIDARITY) to evaluate four candidate treatments (remdesivir, lopinavir/ritonavir, lopinavir/ritonavir/ interferon beta-1a, and chloroquine or hydroxychloroquine) versus standard of care in 18 countries worldwide. RECOVERY trial one of the largest trials to see the efficacy and safety of hydroxychloroquine revealed that they are no clear cut clinical benefit for COVID-19. Other drugs in the SOLIDARTY trial are quite expansive for resource limited countries like Bangladesh. Study Published in the American Journal of Tropical Medicine advocates further research into Ivermectin for COVID-19 Treatment. The spotlight on Ivermectin was brought by Australian researchers from Monash University who demonstrated its efficacy against the SARS-CoV-2 coronavirus in vitro studies. In different study Doxycycline also showed promising results in treatment of COVID 19 infection. It is highly lipophilic antibiotics that are known to chelate zinc component of matrix metalloprotienases (MMP). Corona viruses are known to rely heavily of MMPs for survival, cell infiltration and replication. It also has an anti-inflammatory effect which might be effective in combating cytokine storm of Covid-19 infection. So it have been planned to conduct an experimental clinical trial using combination of ivermectin and doxycycline for treatment of COVID 19 along with the other standard care.

Conditions

Covid19

Keywords

Covid-19, Ivermectin

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Early Clinical Improvement

  Number of patients have clinical improvement as described by WHO and Bangladesh local guideline with 7 days.. 1. Body temperature remains normal for at least 3 days (ear temperature is lower than 37.5 °C). 2. Respiratory symptoms are significantly improved. 3. Lung imaging shows obvious improvement in lesions. 4. There is no co-morbidities or complications which require hospitalization. 5. SpO2, \>93% without assisted oxygen inhalation.

  7 days

• Number of Participants With Late Clinical Recovery

  Number of the patients required more than 12 days for clinical improvement as defined above.

  12 days

Secondary Outcomes (2)

• Number of Patients Having Clinical Deterioration.

  1 month

• Number of Patients Remain Persistently Positive for RT-PCR of Covid-19

  14 days

Study Arms (2)

Ivermectin and Doxycycline

ACTIVE COMPARATOR

Ivermactin 6 mg 2 tab stat, cap Doxycycline 100 mg 1 cap BD 5 days

Drug: Ivermectin and Doxycycline; Drug: Standard of care

Placebo

PLACEBO COMPARATOR

Standard treatment

Drug: Standard of care

Interventions

Ivermectin and Doxycycline DRUG

Ivermectin 6 mg, 2 tab stat and Doxycycline 100 mg twice daily for 5 days

Also known as: Imac and Doxibac

Ivermectin and Doxycycline

Standard of care DRUG

Paracetamol, Vitamin D, Oxygen if indicated, Low molecular weight heparin, dexamethasone if indicated

Ivermectin and Doxycycline; Placebo

Eligibility Criteria

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

You may qualify if:

• COVID-19 infection, confirmed by polymerase chain reaction (PCR) test within 3 days from enrollment
• Only mild and moderate COVID-19 infected cases
• Able to provide informed consent

You may not qualify if:

• Unable to take oral medication
• Pregnant or breast feeding lady
• Patients with severe COVID symptoms or admission in ICU/HDU
• Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) more than 5 upper limit of normal (ULN)
• On non-invasive positive pressure ventilation or mechanical ventilation at time of study entry
• Known hypersensitivity to Doxycycline or ivermectin or its components.

Sponsors & Collaborators

• Dhaka Medical College: lead

Study Sites (1)

Dhaka Medical College

Dhaka, 1000, Bangladesh

Location

Related Publications (1)

• Mahmud R, Rahman MM, Alam I, Ahmed KGU, Kabir AKMH, Sayeed SKJB, Rassel MA, Monayem FB, Islam MS, Islam MM, Barshan AD, Hoque MM, Mallik MU, Yusuf MA, Hossain MZ. Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial. J Int Med Res. 2021 May;49(5):3000605211013550. doi: 10.1177/03000605211013550.

  PMID: 33983065 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Ivermectin; Doxycycline; imidazoleacetic acid; Standard of Care

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)

Macrolides; Polyketides; Lactones; Organic Chemicals; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

We followed up the patients by telephonic (video) interview, which has some inherent drawback for the study. we could not assess viral clearance directly. Only single dose regimen was used. Efficacy might higher if the different regimen would use.

Results Point of Contact

• Title: Dr. Reaz Mahmud, Principal investigator
• Organization: Dhaka Medical College

reazdmc22@yahoo.com

01912270803

Study Officials

• Mahmud Reaz, FCPS

  Assistant Professor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind (The participant and the clinicians/data collectors will be unaware of the treatment the participant receives).The drugs will be labelled with a random code number
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Patient will be randomized 1:1 to placaebo with standard care and combined doxycycline and ivermectin with standard care.

Study Record Dates

• First Submitted: August 19, 2020
• First Posted: August 24, 2020
• Study Start: June 1, 2020
• Primary Completion: August 22, 2020
• Study Completion: September 10, 2020
• Last Updated: October 9, 2020
• Results First Posted: October 9, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: September 2020 to December 2020
• Access Criteria: Person who are investigating covid-19 in various aspects

Locations

BA (1)