Safety and Efficacy of Enoxaparin and Hydroxychloroquine in COVID-19

Evaluation of Safety and Efficacy of Monotherapy Versus Polytherapy of Enoxaparin and Hydroxychloroquine for the Treatment of Covid-19

In this randomized controlled study, two hundred patients with positive PCR and laboratory confirmed COVID-19 will be classified randomly into four groups. The first group is the control group and will be given the conventional treatment of covid-19 only. The second group will be given enoxaparin plus the conventional treatment of Covid-19. The third group will be given hydroxychloroquine (HCQ 400 mg/day) for five days plus the conventional treatment of covid-19. The last group will be given combined therapy of HCQ 400 mg/day and enoxaparin plus the conventional therapy of covid-19

The efficacy will be assessed by the time of undetectable viral RNA, duration of treatment and length of hospital stay. The safety will be assessed by measuring the severity of side effects by following up the patients after treatment.

Study Overview

• Status: Completed
• Conditions: COVID-19 Pandemic
• Intervention / Treatment: Drug: Enoxaparin, Hydroxychloroquine

Detailed Description

Although numerous therapeutic agents for COVID-19 are under investigation, an effective therapy remains a challenge among researchers. To date, hydroxychloroquine has been widely used for covid-19 treatment, despite that its efficacy and safety need further investigations. Coagulopathies are major complications of covid-19 infection, hence prophylactic anticoagulation has been recommended in all hospitalized patients. This study aims to assess the efficacy and safety of Enoxaparin and hydroxychloroquine used separately or combined and added to standard care versus standard care alone in Covid-19 infected patients. An observational study including two hundred patients (98 males, 102 females) with laboratory confirmed covid-19 infection was conducted. Patients admitted to hospital were randomly allocated into four equal treatment groups. The first group received standard Covid-19 therapy, second group received enoxaparin 40mg/day SC for 14 days plus standard Covid-19 therapy, third group received 400 mg/day HCQ for five days plus standard Covid-19 therapy. The fourth group received a combination of 400 mg/day HCQ and enoxaparin plus standard Covid-19 therapy. The clinical disease course progression was evaluated by duration to a negative PCR, length of hospital or ICU stay, and mortality rate. The safety of treatments was evaluated by measuring liver biochemistries (ALT, AST), random blood glucose levels and adverse effects during the 28 days of treatment. Patients on Enoxaparin plus standard Covid-19 therapy significantly showed a decrease in length of hospital stay, ICU admission and mortality compared to all other treatments. However, the duration to both negative PCR and clinical improvement did not find any significance. These findings suggest that enoxaparin treatment was safe, effective, and well tolerated and has a role in decreasing the progression of the disease and its complications while HCQ did not discover any evidence of extra therapeutic benefits over other treatments.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo
    • Banī Suwayf, Cairo, Egypt, 62511
      • Beni-Suef University Teaching Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Laboratory confirmed COVID-19 infection by PCR test within 7 days prior to admission or during admission to hospital, CT or radiographic findings of pneumonia. Clinically suspected infection by symptoms like loss of smell and taste. No medical history that may interfere with treatment or with this clinical trial.

Exclusion Criteria:

• Patient who had allergy or contraindication to HCQ, pregnant and lactating females, and patients with immune diseases, cardiac problem, had history of acute kidney injury or who received multiple cycles of anticoagulants were excluded from the study. Written informed consent was obtained from each participant. All study risks and benefits were thoroughly explained to patients' prior participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group; The control group including 50 patients (n=50) receiving the conventional therapy of Covid-19 adopted by the Egyptian ministry of health for 15 days.	Drug: Enoxaparin, Hydroxychloroquine; To compare efficiency and safety of Enoxaparin and Hydroxychloroquine as monotherapy versus Polytherapy
Active Comparator: Enaxoprin group; The enoxaparin group (n=50) which received 40mg/day SC for 14 days (for patients with normal renal function and body weight between 50 and 100kg) plus the conventional therapy of Covid-19 adopted by the Egyptian ministry of health for 15 days.	Drug: Enoxaparin, Hydroxychloroquine; To compare efficiency and safety of Enoxaparin and Hydroxychloroquine as monotherapy versus Polytherapy
Active Comparator: Hydroxychloroquine group; The HCQ group which received 400 mg/day HCQ for five days plus the conventional therapy of Covid-19 adopted by the Egyptian ministry of health for 15 days(n=50).	Drug: Enoxaparin, Hydroxychloroquine; To compare efficiency and safety of Enoxaparin and Hydroxychloroquine as monotherapy versus Polytherapy
Active Comparator: Enoxaparin plus Hydroxychloroquine group; The HCQ plus Enoxaparin combination group including 50 patients receiving combined therapy of 400 mg/day HCQ for five days and 40mg/day enoxaparin for 14 days plus the conventional therapy of COVID-19 adopted by the Egyptian ministry of health for 15 days	Drug: Enoxaparin, Hydroxychloroquine; To compare efficiency and safety of Enoxaparin and Hydroxychloroquine as monotherapy versus Polytherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of efficacy	The hospital stay of COVID-19 patients	6 monthes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Safety	Mortality of COVID-19 patients	6 monthes

Collaborators and Investigators

• Sponsor: Beni-Suef University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 30, 2021

Study Registration Dates

• First Submitted: April 4, 2022
• First Submitted That Met QC Criteria: April 4, 2022
• First Posted (Actual): April 5, 2022

Study Record Updates

• Last Update Posted (Actual): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Enoxaparin; COVID-19 infection; Hydroxychloroquine; ICU stay
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Enoxaparin; Hydroxychloroquine
• Other Study ID Numbers: REC-H-PhBSU-21013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No