Tofacitinib in Hospitalized Patients With COVID-19 Pneumonia
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| ClinicalTrials.gov Identifier: NCT04469114 |
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Recruitment Status :
Completed
First Posted : July 13, 2020
Last Update Posted : August 9, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Covid19 | Drug: Tofacitinib 10 mg Drug: Placebo | Phase 3 |
COVID-19 is a viral disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that can cause severe pneumonia and ARDS. Respiratory viral load may peak within 5 days after onset, while symptoms are still mild. Many patients rapidly (within 1 to 2 weeks of infection) develop dyspnea and pneumonia and require hospitalization for respiratory support.
Preliminary clinical data from COVID-19 patients indicate that severe symptoms with SARS-CoV-2 infection are associated with an exaggerated immune response driven by interleukin (IL)-6 IL-10, tumor necrosis factor (TNF)α, and other cytokines. The ultimate result is progressive destruction of the alveolar epithelium leading to pneumonia and/or ARDS. Moreover, the exudative phase of ARDS is thought to be due to an influx of myeloid cells (neutrophils and macrophages) and elevations of inflammatory cytokines, with higher levels of both IL-6 and IL-8 levels being correlated with increased mortality. Therefore, immunomodulatory therapy may be beneficial in reducing the deleterious effects of lung inflammation and mitigating progressive lung injury.
Tofacitinib is an inhibitor of Janus kinase (JAKs) 1 and 3, with partial selectivity to JAK 2. Tofacitinib suppresses pro-inflammatory signaling that may be important pathogenetically to progression to more severe lung disease and ARDS in patients with COVID-19.
The purpose of the study is to assess the safety and efficacy of tofacitinib plus standard pharmacologic and supportive measures in treating hospitalized participants with COVID-19 pneumonia.
Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR, who have agreed to participate, will be screened within 72h hours after admission to the hospital to determine eligibility.
Eligible participants will be randomized on Day 1 to the tofacitinib plus standard of care treatment group or the placebo plus standard of care treatment group in a 1:1 ratio, stratified by site. Participants will receive treatment for up to 14 days or until discharge from the hospital, whichever is earlier.
Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety, and laboratory parameters. Follow-up visits will occur on Day 14 and on Day 28.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 289 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-design Trial of Tofacitinib in Hospitalized Participants With COVID-19 Pneumonia |
| Actual Study Start Date : | September 16, 2020 |
| Actual Primary Completion Date : | January 9, 2021 |
| Actual Study Completion Date : | January 9, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Tofacitinib
Tofacitinib 10mg twice daily for 14 days or until hospital discharge
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Drug: Tofacitinib 10 mg
Tofacitinib 10mg administered orally twice daily for 14 days or until hospital discharge |
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Placebo Comparator: Placebo
Placebo twice daily for 14 days or until hospital discharge
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Drug: Placebo
Tofacitinib-matching placebo administered orally twice daily for 14 days or until hospital discharge |
- Death or respiratory failure until Day 28 [ Time Frame: 28 days ]
1, 2 or 3 on the 8-point National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity. The minimum value is 1 (worst outcome) and the maximum value is 8 (best outcome).
- Death.
- Hospitalized, on invasive mechanical ventilation or ECMO.
- Hospitalized, on non-invasive ventilation or high-flow oxygen devices.
- Hospitalized, requiring supplemental oxygen.
- Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise).
- Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care.
- Not hospitalized, limitation on activities and/or requiring home oxygen.
- Not hospitalized, with no limitations on activities.
- National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 [ Time Frame: 14 days ]NIAID ordinal scale of disease severity
- Status of alive and not on mechanical ventilation or ECMO at Day 14 and 28 NIAID ordinal scale of disease severity at Day 14 [ Time Frame: 14 and 28 days ]Categories 3 to 8 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 and Day 28
- Status of requiring supplemental oxygen at Day 28 [ Time Frame: 28 days ]Categories 1 to 4 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity
- Status of being alive and not hospitalized at Day 14 and 28 [ Time Frame: 14 and 28 days ]Categories 7 and 8 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity
- National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 NIAID ordinal scale of disease severity at Day 28 [ Time Frame: 28 days ]NIAID ordinal scale of disease severity
- Number of patients with cure [ Time Frame: 28 days ]Number of patients with resolution of fever, cough, and need for ventilatory or oxygen support.
- Number of patients at the ICU or on ventilatory support at Day 28 [ Time Frame: 28 days ]Number of patients at the ICU or on ventilatory support
- Number of days free from mechanical ventilation at 28 days [ Time Frame: 28 days ]Number of days free from mechanical ventilation
- Number of days in hospital [ Time Frame: 28 days ]Number of days in hospital
- Number of days in ICU [ Time Frame: 28 days ]Number of days in ICU
- Death or respiratory failure at Day 28 [ Time Frame: 28 days ]Categories 1 to 3 in the National Institute of Allergy and Infectious Diseases (NIAID)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male or female participants older than 18 years
- Laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) prior to Day 1.
- Evidence of pneumonia assessed by radiographic imaging (chest x-ray or chest CT scan).
- Hospitalized for less than 72 hours and receiving supportive care for COVID-19
Exclusion Criteria:
- Require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) on Day 1 at the time of randomization
- History of or known current thrombosis. Only if current thrombosis is suspected by the investigator, imaging testing is recommended (per local guidance) to exclude thrombosis.
- Have a personal or first-degree family history of blood clotting disorders.
- Participants who are immunocompromised, with known immunodeficiencies, or taking potent immunosuppressive agents (eg, azathioprine, cyclosporine).
- Participants with any current malignancy or lymphoproliferative disorders that requires active treatment
- Severe hepatic impairment, defined as Child-Pugh class C.
- Severe anemia (hemoglobin <8 g/dL).
- Absolute lymphocyte count <500 cells/mm;
- Absolute neutrophil count <1000 cells/mm.
- Known allergy to tofacitinib.
- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk associated with study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- Suspected or known active systemic bacterial, fungal, or viral infections (with the exception of COVID-19) including but not limited to: active herpes zoster infection; known active tuberculosis or history of inadequately treated tuberculosis; known B hepatitis, C hepatitis, or HIV.
- Have received any of these within 4 weeks prior to the first dose of study intervention: any JAK inhibitors, potent immunosuppressants, or any biologic agents including IL-6 inhibitors (eg, tocilizumab) or IL-1 inhibitors (eg, anakinra) within the past 30 days; any potent cytochrome P450 inducer, such as rifampin, within the past 28 days or 5 half-lives, whichever is longer.
- Have received estrogen-containing contraception or treatment with herbal supplements within 48 hours prior to the first dose of study intervention.
- Have received treatment with corticosteroids equivalent to prednisone or methylprednisolone >20 mg/day for equal or more than 14 consecutive days prior to screening.
- Current participation in other trials.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04469114
Show 17 study locations
| Responsible Party: | Hospital Israelita Albert Einstein |
| ClinicalTrials.gov Identifier: | NCT04469114 |
| Other Study ID Numbers: |
34810620.0.1001.0071 |
| First Posted: | July 13, 2020 Key Record Dates |
| Last Update Posted: | August 9, 2021 |
| Last Verified: | July 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
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COVID-19 Pneumonia Pneumonia, Viral Respiratory Tract Infections Infections Virus Diseases Coronavirus Infections Coronaviridae Infections Nidovirales Infections |
RNA Virus Infections Lung Diseases Respiratory Tract Diseases Tofacitinib Janus Kinase Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |