Safety and Efficacy of Tramadol in COVID-19 Egyptian Patients
Primary Purpose
COVID-19
Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Tramadol
Standard care delivered in the isolation hospitals.
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring COVID-19
Eligibility Criteria
Inclusion Criteria:
- Newly diagnosed symptomatic COVID-19 patients with mild to moderate respiratory manifestations, adults (18-65 Years old), and both sexes.
Exclusion Criteria:
- Patients with abnormal liver function (ALT, AST), chronic kidney disease or dialysis (CrCl< 30 ml/min)
- Pregnant women or women who are breastfeeding
- Immunocompromised patients taking medication upon screening
- Subjects with comorbid condition like hypertension, cardiovascular disease, diabetes mellites, asthma, COPD, malignancy
- Patients having allergy to Hydroxychloroquine and/or Nitazoxanide
- Patients with contraindication towards the study medication including retinopathy, G6PD deficiency and QT prolongation.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Tramadol
standard care
Arm Description
tramadol 100 mg twice daily for 10 days
standard care plus (placebo twice daily for 10 days).
Outcomes
Primary Outcome Measures
Number of COVID-19 PCR negative cases
PCR analysis of nasal swabs from COVID-19 patients
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04454307
Brief Title
Safety and Efficacy of Tramadol in COVID-19 Egyptian Patients
Official Title
Safety and Efficacy of Tramadol Adjuvant Therapy to Standard Care for COVID-19 Egyptian Patients: A Randomized Double Blind Controlled Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Unknown status
Study Start Date
July 2020 (Anticipated)
Primary Completion Date
August 2020 (Anticipated)
Study Completion Date
October 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tanta University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The rationale of the use of tramadol for COVID-19 patients is attributed to its anti-inflammatory, hypocagulatory, antioxidant, cardio-protective, analgesic, antitussive, bactericidal and antidepressant effect.
Detailed Description
Background and Rationale:
T cells play a critical role in antiviral immunity, their level was dramatically reduced in COVID-19 patients. There is a negative correlation between T cell numbers and cytokines serum level in COVID-19 patients. In those patients, there is up-regulation of inflammatory cytokines including interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, and interferon γ. This makes the use of tramadol reasonable in such patients because it has anti-inflammatory effect decreasing plasma level of TNF-α after treatment with a dose of 100 mg every 12 hours for 10 days, which may result in a subsequent increase in T cell numbers.
Besides, COVID-19 patients with acute respiratory failure present with severe hypercoagulability due to hyperfibrinogenemia resulting in increased fibrin formation and polymerization that may predispose to thrombosis. It has been reported that tramadol has a hypocoagulable effect in the blood of women with gynecologic malignancies. Consequently, tramadol may be useful for patients who have a tendency toward a hypercoagulable status and thromboembolic complications. Moreover, tramadol could affect hemostatic parameters in favor of bleeding tendency in rats.
On the other hand, the severity and mortality risk of COVID-19 have been associated with the age. This age-related mortality is attributed to the shortage of antioxidant mechanisms and increased oxidative damage. Tramadol increased the antioxidant enzymes superoxide dismutase and glutathione peroxidase while diminished the oxidative stress marker malondialdehyde in testicular ischemia-reperfusion injury in rats. Owing to its antioxidant properties, tramadol could reduce complications in COVID-19 patients.
Moreover, tramadol was reported to significantly lower lactate dehydrogenase (LDH) level and to provide a cardio-protective effect. This property of tramadol seems beneficial since it was found that, about 60% of COVID-19 patients are presented with elevated LDH levels. Tramadol has also antitussive property. Tramadol is a unique analgesic offering moderate, dose-related pain relief through its action at multiple sites. In contrast to pure opioid agonists, it has a low risk of respiratory depression, tolerance, and dependence. Previous studies confirmed that tramadol dependence may occur when it is used daily for more than a few weeks/months.
More interestingly, patients infected with COVID-19 may experience intense emotional and behavioral reactions, such as fear, loneliness, anxiety, insomnia, or anger. These conditions can be especially prevalent in quarantined patients. Tramadol is a centrally acting analgesic drug with a dual mechanism of action: binding to μ-opioid receptors and the inhibition of serotonin and norepinephrine reuptake. Through its ability to inhibit serotonin and norepinephrine reuptake, tramadol may exhibit antidepressant activity. In this context, the analgesic and antidepressant effects of tramadol may favor its use for COVID-19 patients. Tramadol also was found to have dose- and time-dependent bactericidal activity against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa pathogens in vitro.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
COVID-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
A randomized Double Blind Controlled Clinical Trial
Masking
ParticipantCare Provider
Masking Description
A randomized Double Blind Controlled Clinical Trial
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tramadol
Arm Type
Experimental
Arm Description
tramadol 100 mg twice daily for 10 days
Arm Title
standard care
Arm Type
Active Comparator
Arm Description
standard care plus (placebo twice daily for 10 days).
Intervention Type
Drug
Intervention Name(s)
Tramadol
Other Intervention Name(s)
tramal
Intervention Description
tramadol 100 mg twice daily for 10 days
Intervention Type
Other
Intervention Name(s)
Standard care delivered in the isolation hospitals.
Other Intervention Name(s)
nasal oxygen
Intervention Description
Oxygen ventilation.
Primary Outcome Measure Information:
Title
Number of COVID-19 PCR negative cases
Description
PCR analysis of nasal swabs from COVID-19 patients
Time Frame
10 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Newly diagnosed symptomatic COVID-19 patients with mild to moderate respiratory manifestations, adults (18-65 Years old), and both sexes.
Exclusion Criteria:
Patients with abnormal liver function (ALT, AST), chronic kidney disease or dialysis (CrCl< 30 ml/min)
Pregnant women or women who are breastfeeding
Immunocompromised patients taking medication upon screening
Subjects with comorbid condition like hypertension, cardiovascular disease, diabetes mellites, asthma, COPD, malignancy
Patients having allergy to Hydroxychloroquine and/or Nitazoxanide
Patients with contraindication towards the study medication including retinopathy, G6PD deficiency and QT prolongation.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nahla Elashmawy, PhD
Phone
201116721982
Email
nahla.elashmawi@pharm.tanta.edu.eg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nahla Elashmawy, PhD
Organizational Affiliation
Tanta University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
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Safety and Efficacy of Tramadol in COVID-19 Egyptian Patients
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