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Effect of Pioglitazone on T2DM Patients With COVID-19 (PIOQ8)

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ClinicalTrials.gov Identifier: NCT04604223
Recruitment Status : Recruiting
First Posted : October 27, 2020
Last Update Posted : March 17, 2021
Sponsor:
Collaborators:
Ministry of Health, Kuwait
Texas Diabetes Institute
Kuwait University
Information provided by (Responsible Party):
Dasman Diabetes Institute

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Covid19 Type 2 Diabetes Drug: Pioglitazone 45 mg Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1506 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Pioglitazone on Inflammatory Response and Clinical Outcome in T2DM Patients With COVID-19
Actual Study Start Date : January 18, 2021
Estimated Primary Completion Date : June 29, 2021
Estimated Study Completion Date : June 29, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Pioglitazone 45 mg
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

Placebo Comparator: 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.
Drug: Pioglitazone 45 mg
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




Primary Outcome Measures :
  1. HsCRP level [ Time Frame: 4 weeks ]
    Difference from baseline to 4 weeks in inflammatory response between subjects receiving pioglitazone versus placebo measured as plasma hsCRP level.

  2. Difference in the incidence at 4 weeks of a composite outcome comprised of: [ Time Frame: 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.


Secondary Outcome Measures :
  1. Number of days free of mechanical ventilation [ Time Frame: 4 weeks ]
  2. Number of days in the ICU [ Time Frame: 4 weeks ]
  3. Duration of hospitalization [ Time Frame: 4 weeks ]
  4. Change from baseline in qSOFA score [ Time Frame: 4 Weeks ]
  5. Change from baseline in SO2/FiO2 [ Time Frame: 4 Weeks ]
  6. Difference in respiratory rate [ Time Frame: 4 weeks ]
    Difference in respiratory rate, measured as the area under the curve of respiratory rate over time from baseline to week 4

  7. Incidence at 4 weeks of a composite of extrapulmonary disease comprised of : [ Time Frame: 4 weeks ]
    (a) myocardial disease measured as troponin I above the normal limit at any time during hospitalization, (b) neurologic disease manifested as TIA, or symptoms of peripheral or central neurologic deficient at anytime during hospitalization, (c) renal failure measured as > 50% decrease in eGFR



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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. 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
  3. COVID-19 infection confirmed with PCR test
  4. Age 21-85 years
  5. Patients of both sexes will be included
  6. 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).
  7. 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

Exclusion Criteria:

  1. T1DM
  2. Absence of confirmation of COVID-19 infection
  3. Age <21 years
  4. Presence of heart failure (LVEF<40%) or a history of hospitalization for heart failure
  5. 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
  6. Patient on mechanical ventilation or patients whose clinical condition requires mechanical ventilation in the following 24 hours.
  7. Patients not expected to survive > 48 hours
  8. Patients receiving pioglitazone for the management of their diabetes
  9. Patients participating in other research study will be excluded
  10. Pregnant women will be excluded from the study

Information from the National Library of Medicine

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): NCT04604223


Contacts
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Contact: Mohamed Abu-farha, PhD 96560660804 mohamed.abufarha@dasmaninstitute.org
Contact: Thamer Alessa, MD 96599877855 thamer.alessa@dasmaninstitute.org

Locations
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Kuwait
Al-Amiri Hospital Recruiting
Kuwait City, (Pick From List), Kuwait, 40000
Contact: Abdulnabi Alatar, MD         
Contact: Hawra Almatrouk, MD         
Sub-Investigator: Dina Jamal, MD         
Jaber Al Ahmad Al Sabah Hospital Recruiting
Kuwait City, (Pick From List), Kuwait, 40000
Contact: Thamer Alessa, MD         
Contact: Hiba Humedi, MD         
Mishrif Field Hospital Recruiting
Kuwait City, (Pick From List), Kuwait, 40000
Contact: Ali Alandaleeb, MD         
Mubarak Al-Kabeer Hospital Recruiting
Kuwait City, (Pick From List), Kuwait, 40000
Contact: Ahmad Esmaeel, MD         
Qatar
Hamad Medical Corporation Recruiting
Doha, Qatar
Contact: Amin JAYYOUSI, MD         
Contact: Khalid Baagar, MD         
Sponsors and Collaborators
Dasman Diabetes Institute
Ministry of Health, Kuwait
Texas Diabetes Institute
Kuwait University
Investigators
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Principal Investigator: Fahd Al-Mulla, PhD Dasman Diabetes Institute
Principal Investigator: Thamer Alessa, MD Dasman Diabetes Institute. Ministry of Health, Kuwait
Principal Investigator: Mohamed Abu-farha Dasman Diabetes Institute
Principal Investigator: Muhammed Abdul-Ghani, MD/PhD Texas Diabetes Institute
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Responsible Party: Dasman Diabetes Institute
ClinicalTrials.gov Identifier: NCT04604223    
Other Study ID Numbers: RA HM-2020- 011
First Posted: October 27, 2020    Key Record Dates
Last Update Posted: March 17, 2021
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs