COVID-19Phase 1/2NCT04454307
Safety and Efficacy of Tramadol in COVID-19 Egyptian Patients
A Phase 1/2 study testing Tramadol in people with COVID-19, run by Tanta University.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Tramadol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Jul 2020to Oct 2020
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed symptomatic COVID-19 patients with mild to moderate respiratory manifestations, adults (18-65 Years old), and both sexes.
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Safety and Efficacy of Tramadol Adjuvant Therapy to Standard Care for COVID-19 Egyptian Patients: A Randomized Double Blind Controlled Clinical Trial
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.
Read the 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
- Being tested
- Tramadol, Standard care delivered in the isolation hospitals.
- Keywords
- COVID-19
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TramadolDrug
Also called tramal
tramadol 100 mg twice daily for 10 days
Standard care delivered in the isolation hospitals.Other
Also called nasal oxygen
Oxygen ventilation.
| Study group | Role | What they receive |
|---|---|---|
| Tramadol | Experimental | tramadol 100 mg twice daily for 10 days Receives: Drug: Tramadol |
| standard care | Active comparator | standard care plus (placebo twice daily for 10 days). Receives: Other: Standard care delivered in the isolation hospitals. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of COVID-19 PCR negative cases
PCR analysis of nasal swabs from COVID-19 patients
Measured: 10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2020
- Study startJul 2020 (estimated)
- Primary completionAug 2020 (estimated)
- Study completionOct 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Tanta UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized Double Blind Controlled Clinical Trial
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tanta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Dr. Nahla El-Ashmawy, Tanta University
- Investigators
- Nahla Elashmawy, PhD, Principal investigator, Tanta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04454307
- Sponsor's protocol ID
- TRAM/COVID19
- Status last verified
- Jun 2020
- First submitted
- 29 Jun 2020
- Last updated
- 2 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Tramadol Adjuvant Therapy to Standard Care for COVID-19 Egyptian Patients: A Randomized Double Blind Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT04454307
- Acronym / sponsor ID
- TRAM/COVID19
- Conditions
- COVID-19
- Keywords
- COVID-19
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Tanta UniversityUniversity, hospital or other
- Study start
- Jul 2020 (estimated)
- Primary completion
- Aug 2020 (estimated)
- Study completion
- Oct 2020 (estimated)
- First posted
- 1 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- A randomized Double Blind Controlled Clinical Trial
| Arm | Type | Receives |
|---|---|---|
| Tramadol | Experimental | Drug: Tramadoltramadol 100 mg twice daily for 10 days |
| standard care | Active comparator | Other: Standard care delivered in the isolation hospitals.standard care plus (placebo twice daily for 10 days). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Newly diagnosed symptomatic COVID-19 patients with mild to moderate respiratory manifestations, adults (18-65 Years old), and both sexes.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TramadolAlso: tramaltramadol 100 mg twice daily for 10 days | Drug | Tramadol |
| Standard care delivered in the isolation hospitals.Also: nasal oxygenOxygen ventilation. | Other | standard care |
Primary outcome
Number of COVID-19 PCR negative cases
Time frame: 10 days
PCR analysis of nasal swabs from COVID-19 patients
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nahla Elashmawy, PhD principal investigator
Tanta University
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tramadol in people with COVID-19, run by Tanta University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nahla Elashmawy, PhD (201116721982, nahla.elashmawi@pharm.tanta.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of COVID-19 PCR negative cases (time frame: 10 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2020.