Safety and Efficacy of Tramadol in COVID-19 Egyptian Patients

NCT ID: NCT04454307

Last Updated: 2020-07-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-31
• Study Completion Date: 2020-10-31

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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Tramadol

tramadol 100 mg twice daily for 10 days

Group Type: EXPERIMENTAL

Tramadol

Intervention Type: DRUG

tramadol 100 mg twice daily for 10 days

standard care

standard care plus (placebo twice daily for 10 days).

Group Type: ACTIVE_COMPARATOR

Standard care delivered in the isolation hospitals.

Intervention Type: OTHER

Oxygen ventilation.

Interventions

Tramadol

tramadol 100 mg twice daily for 10 days

Intervention Type: DRUG

Standard care delivered in the isolation hospitals.

Oxygen ventilation.

Intervention Type: OTHER

Other Intervention Names

tramal; nasal oxygen

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tanta University

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Nahla El-Ashmawy

Dean of Faculty of Pharmacy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nahla Elashmawy, PhD

Role: PRINCIPAL_INVESTIGATOR

Tanta University

Central Contacts

Nahla Elashmawy, PhD

Role: CONTACT

nahla.elashmawi@pharm.tanta.edu.eg

201116721982

Other Identifiers

TRAM/COVID19

Identifier Type: -

Identifier Source: org_study_id