Covid19NCT04739345
Effect of Pentoxifylline on Prognosis of Coronavirus Disease 2019 (COVID- 19) Infection
A study testing Pentoxifylline in people with Covid19 and Corona Virus Infection, run by Ain Shams University at 1 site in Egypt.
Trial summary
Coronavirus disease 2019 (COVID-19) remains a threatening pandemic, due to its rapid transmission, uncertain risk factors for progression that lead to its lethality and yet unsatisfactory antiviral therapy or prophylaxis. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Covid19, Corona Virus Infection, Cytokine Storm
- What is being tested?
- Pentoxifylline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Dec 2020to 1 Oct 2022
- Phase
- Interventional
- 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
- Age 18 to 65 years.
- COVID-19 hospitalized patients with pneumonia proved by chest X-ray or CT scan.
- Confirmed infection with COVID-19 virus using RT-PCR or strongly suspected to be infected with pending confirmation studies.
- Have acute respiratory distress syndrome (ARDS).
- Having either peripheral capillary oxygen saturation (SpO2) ≤ 94% ambient air, or a partial oxygen pressure (PaO2) to fraction of inspired oxygen (FiO2) ratio ≤ 300 mmHg.
Who cannot join
- Age greater than 85 years-old
- Creatinine clearance (CrCl) < 10ml/min.
- Severe circulatory shock with a dose of norepinephrine higher than 1.0 μg/kg/min.
- Pregnant women.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Pentoxifylline on Immune-inflammation Index for Predicting Prognosis of Coronavirus Disease 2019 (COVID- 19) Infection
Coronavirus disease 2019 (COVID-19) remains a threatening pandemic, due to its rapid transmission, uncertain risk factors for progression that lead to its lethality and yet unsatisfactory antiviral therapy or prophylaxis. The respiratory system remains the most frequently affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2), with patients either presenting mild illness as well as more severe complications such as acute respiratory distress syndrome (ARDS) that necessitates admission in Intensive Care Units (ICU). Unfortunately, the remaining patients progress to a second phase-called the inflammatory stage-featuring ARDS, thromboembolic events, and myocardial acute injury. These clinical exacerbation latter predicts poor prognosis associated with an exacerbation of the immune system cascade; a phenomenon known as "cytokine storm". In the context of COVID-19, the hyper inflammation diagnostic criteria are partly defined. Early studies of patients with COVID-19 established independent associations between biomarkers of inflammation, such as C-reactive protein, interleukin [IL]-6, ferritin and D-dimer, and severe disease states that require respiratory support or result in death.
The aim of this study was to identify practical blood immune- inflammatory biomarker / ratio that could be used alternatively to IL-6 for predicting severity of coronavirus disease 2019 (COVID- 19) in clinical practice.
Another aim is to unveil the association of the pro-inflammatory profile as categorized by the IL-6 levels in patients infected by SARS-COV-2, with disease severity and outcomes of COVID -19.
Read the detailed description
Recent research confirmed that levels of IL-6 seem are associated with COVID-19 induced inflammatory response, respiratory failure, needing for mechanical ventilation and/or intubation and mortality. The importance of identifying Il-6 as a biomarker lies in the potential use of antibody against IL-6 such as tocilizumab, which is currently used in the treatment protocol of covid-19. The authors shared an encouraging experience of utilizing tocilizumab medication, particularly in patients at risk of developing chemokine storm secondary to COVID-19. IL-6, a chemokine, is an important biomarker of inflammation and has been shown in studies as an important predictor of severe COVID-19. IL-6 is responsible for elevation of acute phase reactants, such as C-reactive protein, serum amyloid A, fibrinogen, and hepcidin, and inhibition of albumin synthesis. The dysregulated production of IL-6 has been attributed to autoimmunity and chronic inflammation.
We performed a systematic review and meta analysis to compare IL-6 in severe and non severe patients. In clinical practice, it remains crucial to develop a scoring system that includes IL-6 to assist clinicians in early recognition of patients at risk for developing severe disease.
Circulating biomarker like neutrophil (NEU)-to-lymphocyte (LYM) ratio (NLR) as well as other ratios are used to represent inflammation and the immune status and are considered a potential predictor for the prognosis of COVID-19 patients. Interestingly clinical scores like the CALL score (C = comorbidity, A= age, L = lymphocyte count, L = lactate dehydrogenase (LDH)) have been used for predicting progression towards clinical worsening.
Adding IL-6 levels to the CALL score proved to improve its predictive power and make treatment more appropriate, especially in patients for whom decision whether to treat or not with IL-6 inhibitors such as tocilizumab is required. It should be recognized that the CALL-IL-6 score could be difficult to reproduce in low- and medium-income countries due to costs of IL-6 dosage.
Aim of the Study
- Identify new blood immune inflammatory biomarker / ratio that could be used alternatively to IL-6 for predicting severity of coronavirus disease 2019 (COVID- 19) in clinical practice.
- Evaluate the influence of the pro-inflammatory profile on clinical outcomes and therapeutic efficacy as categorized by the IL-6 levels in patients infected by SARS-COV-2.
- Assess potential associations with other blood inflammatory biomarker and the impact of the inflammatory status on clinical outcomes.
- Conditions
- Covid19, Corona Virus Infection, Cytokine Storm
- Being tested
- Pentoxifylline
- Keywords
- COVID-19, Cytokine Storm, Interleukin-6
- Medical subject headings
- COVID-19, Coronavirus Infections, Cytokine Release Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PentoxifyllineDrug
400 mg of pentoxifylline orally TID with the standard COVID-19 protocol of the Egyptian Ministry of Health
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Active comparator | Non-severe patients should meet all following conditions: (1) Epidemiology history, (2) Fever or other respiratory symptoms, (3) Typical CT image abnormities of viral pneumonia, and (4) Positive result of RT-PCR for SARS-CoV-2 RNA. Receives: Drug: Pentoxifylline |
| Group 2 | Placebo comparator | Severe patients should meet at least one of the following conditions: (1) Shortness of breath, RR ≥ 30 times/min, (2) Oxygen saturation (Resting state) ≤ 93%, (3) PaO2/FiO2 ≤ 300 mmHg. Receives: Drug: Pentoxifylline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in patients' clinical status
Change in clinical status will be assessed daily using six category ordinal scale. The categories were defined as follows: 1) patient discharged, 2) hospitalization not requiring supplemental oxygen, 3) hospitalization requiring supplemental low-flow oxygen, 4) hospitalization requiring high-flow supplemental oxygen, 5) hospitalization requiring invasive mechanical ventilation, 6) death.
Measured: Two weeks
Time to increase in oxygenation
Time to increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2
Measured: 48 hours
Duration of hospitalization
Length of hospital stay
Measured: Two weeks
In hospital mortality
Death occurrence during hospitalization
Measured: Two weeks
Secondary outcomes (5)
Incidence of non-invasive mechanical ventilation
Need for non-invasive mechanical ventilation
Measured: Two weeks
Duration of non-invasive mechanical ventilation
Time required on non-invasive mechanical ventilation
Measured: Two weeks
Incidence of invasive mechanical ventilation
Need for invasive mechanical ventilation
Measured: Two weeks
Duration of invasive mechanical ventilation
Time required on invasive mechanical ventilation
Measured: Two weeks
Occurrence of secondary infection
Occurrence of sepsis
Measured: Two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2021
- Study start1 Dec 2020
- Primary completion1 Jun 2021
- Study completion1 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by Ain Shams 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Collaborators
- Misr International University
- Responsible party
- Principal investigator, Neven Sarhan, Misr International University
- Investigators
- Neven Sarhan, PhD, Principal investigator, Misr International University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04739345
- Sponsor's protocol ID
- COVID-Pentoxifylline
- Status last verified
- Feb 2023
- First submitted
- 3 Feb 2021
- Last updated
- 9 Feb 2023
- 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 9 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Pentoxifylline on Immune-inflammation Index for Predicting Prognosis of Coronavirus Disease 2019 (COVID- 19) Infection
- ClinicalTrials.gov ID
- NCT04739345
- Acronym / sponsor ID
- COVID-Pentoxifylline
- Conditions
- Covid19, Corona Virus Infection, Cytokine Storm
- Keywords
- COVID-19, Cytokine Storm, Interleukin-6
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Collaborators
- Misr International University
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 1 Oct 2022 (actual)
- First posted
- 4 Feb 2021 (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.
Coronavirus disease 2019 (COVID-19) remains a threatening pandemic, due to its rapid transmission, uncertain risk factors for progression that lead to its lethality and yet unsatisfactory antiviral therapy or prophylaxis. The respiratory system remains the most frequently affected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2), with patients either presenting mild illness as well as more severe complications such as acute respiratory distress syndrome (ARDS) that necessitates admission in Intensive Care Units (ICU). Unfortunately, the remaining patients progress to a second phase-called the inflammatory stage-featuring ARDS, thromboembolic events, and myocardial acute injury. These clinical exacerbation latter predicts poor prognosis associated with an exacerbation of the immune system cascade; a phenomenon known as "cytokine storm". In the context of COVID-19, the hyper inflammation diagnostic criteria are partly defined. Early studies of patients with COVID-19 established independent associations between biomarkers of inflammation, such as C-reactive protein, interleukin [IL]-6, ferritin and D-dimer, and severe disease states that require respiratory support or result in death.
The aim of this study was to identify practical blood immune- inflammatory biomarker / ratio that could be used alternatively to IL-6 for predicting severity of coronavirus disease 2019 (COVID- 19) in clinical practice.
Another aim is to unveil the association of the pro-inflammatory profile as categorized by the IL-6 levels in patients infected by SARS-COV-2, with disease severity and outcomes of COVID -19.
Detailed description
Recent research confirmed that levels of IL-6 seem are associated with COVID-19 induced inflammatory response, respiratory failure, needing for mechanical ventilation and/or intubation and mortality. The importance of identifying Il-6 as a biomarker lies in the potential use of antibody against IL-6 such as tocilizumab, which is currently used in the treatment protocol of covid-19. The authors shared an encouraging experience of utilizing tocilizumab medication, particularly in patients at risk of developing chemokine storm secondary to COVID-19. IL-6, a chemokine, is an important biomarker of inflammation and has been shown in studies as an important predictor of severe COVID-19. IL-6 is responsible for elevation of acute phase reactants, such as C-reactive protein, serum amyloid A, fibrinogen, and hepcidin, and inhibition of albumin synthesis. The dysregulated production of IL-6 has been attributed to autoimmunity and chronic inflammation.
We performed a systematic review and meta analysis to compare IL-6 in severe and non severe patients. In clinical practice, it remains crucial to develop a scoring system that includes IL-6 to assist clinicians in early recognition of patients at risk for developing severe disease.
Circulating biomarker like neutrophil (NEU)-to-lymphocyte (LYM) ratio (NLR) as well as other ratios are used to represent inflammation and the immune status and are considered a potential predictor for the prognosis of COVID-19 patients. Interestingly clinical scores like the CALL score (C = comorbidity, A= age, L = lymphocyte count, L = lactate dehydrogenase (LDH)) have been used for predicting progression towards clinical worsening.
Adding IL-6 levels to the CALL score proved to improve its predictive power and make treatment more appropriate, especially in patients for whom decision whether to treat or not with IL-6 inhibitors such as tocilizumab is required. It should be recognized that the CALL-IL-6 score could be difficult to reproduce in low- and medium-income countries due to costs of IL-6 dosage.
Aim of the Study
- Identify new blood immune inflammatory biomarker / ratio that could be used alternatively to IL-6 for predicting severity of coronavirus disease 2019 (COVID- 19) in clinical practice.
- Evaluate the influence of the pro-inflammatory profile on clinical outcomes and therapeutic efficacy as categorized by the IL-6 levels in patients infected by SARS-COV-2.
- Assess potential associations with other blood inflammatory biomarker and the impact of the inflammatory status on clinical outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Active comparator | Drug: PentoxifyllineNon-severe patients should meet all following conditions: (1) Epidemiology history, (2) Fever or other respiratory symptoms, (3) Typical CT image abnormities of viral pneumonia, and (4) Positive result of RT-PCR for SARS-CoV-2 RNA. |
| Group 2 | Placebo comparator | Drug: PentoxifyllineSevere patients should meet at least one of the following conditions: (1) Shortness of breath, RR ≥ 30 times/min, (2) Oxygen saturation (Resting state) ≤ 93%, (3) PaO2/FiO2 ≤ 300 mmHg. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 to 65 years.
- COVID-19 hospitalized patients with pneumonia proved by chest X-ray or CT scan.
- Confirmed infection with COVID-19 virus using RT-PCR or strongly suspected to be infected with pending confirmation studies.
- Have acute respiratory distress syndrome (ARDS).
- Having either peripheral capillary oxygen saturation (SpO2) ≤ 94% ambient air, or a partial oxygen pressure (PaO2) to fraction of inspired oxygen (FiO2) ratio ≤ 300 mmHg.
Key exclusion criteria (4 listed)
- Age greater than 85 years-old
- Creatinine clearance (CrCl) < 10ml/min.
- Severe circulatory shock with a dose of norepinephrine higher than 1.0 μg/kg/min.
- Pregnant women.
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 |
|---|---|---|
| Pentoxifylline400 mg of pentoxifylline orally TID with the standard COVID-19 protocol of the Egyptian Ministry of Health | Drug | Group 1, Group 2 |
Primary outcome
Change in patients' clinical status
Time frame: Two weeks
Change in clinical status will be assessed daily using six category ordinal scale. The categories were defined as follows: 1) patient discharged, 2) hospitalization not requiring supplemental oxygen, 3) hospitalization requiring supplemental low-flow oxygen, 4) hospitalization requiring high-flow supplemental oxygen, 5) hospitalization requiring invasive mechanical ventilation, 6) death.
Time to increase in oxygenation
Time frame: 48 hours
Time to increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2
Duration of hospitalization
Time frame: Two weeks
Length of hospital stay
In hospital mortality
Time frame: Two weeks
Death occurrence during hospitalization
5 secondary outcomes
Incidence of non-invasive mechanical ventilation
Time frame: Two weeks
Duration of non-invasive mechanical ventilation
Time frame: Two weeks
Incidence of invasive mechanical ventilation
Time frame: Two weeks
Duration of invasive mechanical ventilation
Time frame: Two weeks
Occurrence of secondary infection
Time frame: Two weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2023.
- 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.
Neven Sarhan, PhD principal investigator
Misr International University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pentoxifylline in people with Covid19 and Corona Virus Infection, run by Ain Shams University at 1 site in Egypt.
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 5 inclusion and 4 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: finished, as of the sponsor's last update on 9 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in patients' clinical status (time frame: Two weeks). The study lists 4 primary outcomes in all. 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 9 Feb 2023.