Effect of Pioglitazone on Inflammatory Response and Clinical Outcome in T2DM Patients With COVID-19
试验速览
- 阶段
- 4 期
- 入组人数
- 1,506
- 试验地点
- 5
- 主要终点
- Difference in the incidence at 4 weeks of a composite outcome comprised of:
研究概览
简要总结
Approximately 10-15% of patients infected with COVID-19 develop severe illness characterized by respiratory distress, increased risk of clotting disease, myocardial damage, stroke and mortality. Subjects with Type 2 diabetes (T2DM) are at increased risk for severe COVID-19 disease. Exuberant inflammatory and immune responses were suggested as the etiology responsible for the development of severe COVID-19 disease. The increased chronic inflammatory state characteristic of T2DM could contribute to the increased risk of severe COVID-19 disease in T2DM patients. Therefore, its possible that anti-inflammatory therapy will reduce the risk of severe COVID-19 disease. Consistent with this assumption, a recent study has reported that steroid therapy improves the outcome in patients with severe COVID-19 disease.
The medication pioglitazone is a strong insulin sensitizer that reduces plasma glucose concentrations in T2DM patients. In addition to improving insulin sensitivity, several studies have demonstrated that pioglitazone reduces chronic inflammation in T2DM patients, which is manifested in a decrease in TNF-alpha, interleukin, hs CRP, leptin and other inflammatory markers in T2DM treated with pioglitazone. Further, pioglitazone enhances the plasma level of anti-inflammatory agents. For example, the plasma level of 15-epi-lipoxin A, a lipid mediator with strong anti-inflammatory and inflammation-resolving effects that has been reported to neutralize RNA coated viruses, is significantly elevated by pioglitazone treatment in T2DM patients. Therefore, we hypothesize that administering pioglitazone to T2DM patients who have moderate-to-severe COVID-19 will improve the clinical outcome of their COVID-19 disease.
详细描述
The study design is prospective, double blind, placebo-controlled trial aims to examine the effect of pioglitazone on inflammatory markers and clinical outcome in T2DM patients infected with COVID-19. 1506 T2DM patients with proven COVID-19 infection (positive swab) and at least one COVID-19 symptom will be randomized to receive in a double blind fashion pioglitazone or placebo for 28 days. Inflammatory response and a composite of clinical outcome will be measured at 3, 7, 14, 21 and 28 days (or time of discharge) after initiating therapy.
Study Design
- Upon admission, subjects will be evaluated for inclusion and exclusion criteria. Eligible subjects will be consented.
- After consenting, medical history and vital signs will be done including ECG and chest X-ray.
- Blood for the following parameters (Panel 1, which are routinely measured for the management of COVID-19 patients) will be sent for measurement in the clinical lab: CBC, Full chemistry panel including LFT and RFT, lipid profile, blood gases, HbA1c, hsCRP, Troponin I, coagulation screen, D-Dimers, and Ferritin.
Study Intervention:
After completing baseline studies, subjects will be randomized in a double-blind fashion to receive: (1) pioglitazone, or (2) placebo. The study intervention will be introduced every morning at the same time for 4 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •T2DM according to the ADA criteria. Patients with long standing diabetes as well as patients with new onset diabetes will be recruited. Patients receiving glucocorticoids for treatment of COVID-19 and manifest plasma glucose levels consistent with diabetes diagnosis also will be included
- •Patients can be drug naïve, receiving oral antihyperglycemic therapy (except pioglitazone), GLP-1 RA or insulin therapy will be allowed to participate in the study
- •COVID-19 infection confirmed with PCR test
- •Age 21-85 years
- •Patients of both sexes will be included
- •In addition to diabetes and COVID-19 diagnoses, patients should manifest at least one of COVID-19 symptoms (Fever, Chills, Headache, Rhinorreah, Cough (dry or with sputum), Sore Throat, shortness of breath, Hemoptysis, Altered mentation, Fatigue/Malaise, Myalgia, Nausea/Vomiting, Diarrhea, Anosmia, Chest pain).
- •Patient receiving other anti-inflammatory therapy for their routine COVID-19 care (e.g. hydroxychloroquine), or antiviral therapy (e.g. remdesivire) will be included in the study and will be evenly randomized amongst the two treatment groups
排除标准
- •Absence of confirmation of COVID-19 infection
- •Age <21 years
- •Presence of heart failure (LVEF<40%) or a history of hospitalization for heart failure
- •Use of diuretics (furosemide or aldactone) for heart disease usually for heart failure. Patients with hypertension receiving diuretic therapy (usually thiazide) will be included in the study
- •Patient on mechanical ventilation or patients whose clinical condition requires mechanical ventilation in the following 24 hours.
- •Patients not expected to survive > 48 hours
- •Patients receiving pioglitazone for the management of their diabetes
- •Patients participating in other research study will be excluded
- •Pregnant women will be excluded from the study
研究组 & 干预措施
Pioglitazone
Pioglitazone will be started at 45 mg/day dose for 10 days, after 10 days, the dose will be reduced to 30 mg/day to minimize possible adverse events. The treatment will be continued for 4 weeks (28 days) total.
干预措施: Pioglitazone 45 mg (Drug)
Placebo
Placebo tablets at 45 mg/day will be given for 10 days, after 10 days, the tablets will be reduced to 30 mg/day. The treatment will be continued for 4 weeks (28 days) total.
干预措施: Pioglitazone 45 mg (Drug)
结局指标
主要结局
Difference in the incidence at 4 weeks of a composite outcome comprised of:
时间窗: 4 weeks
1) requirement for mechanical ventilation (invasive \[with tracheal tube\] or non-invasive); 2) myocardial damage measured as plasma troponin I level \> 3 times the upper normal limit; or 3) death.
HsCRP level
时间窗: 4 weeks
Difference from baseline to 4 weeks in inflammatory response between subjects receiving pioglitazone versus placebo measured as plasma hsCRP level.
次要结局
- Number of days free of mechanical ventilation(4 weeks)
- Number of days in the ICU(4 weeks)
- Change from baseline in SO2/FiO2(4 Weeks)
- Duration of hospitalization(4 weeks)
- Change from baseline in qSOFA score(4 Weeks)
- Difference in respiratory rate(4 weeks)
- Incidence at 4 weeks of a composite of extrapulmonary disease comprised of :(4 weeks)