Back to resultsEfficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19
Primary Purpose
COVID 19, Coronavirus, Diabetes Mellitus, Type 2
Status
Terminated
Phase
Phase 3
Locations
Israel
Study Type
Interventional
Intervention
Linagliptin 5 MG
Sponsored by
About this trial
This is an interventional treatment trial for COVID 19
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years.
- History of or type 2 diabetes mellitus or a diagnosis of type 2 diabetes during hospitalization.
- Confirmation of infection with SARS-CoV-2 by PCR testing.
- Patients within 10 days from symptom onset or patients within 48 hours after laboratory diagnosis (SARS-CoV-2 PCR).
Exclusion Criteria:
- WHO COVID-19 Ordinal Scale for Clinical Improvement ≥ 6.
- Respiratory failure requiring mechanical ventilation prior to randomization.
- Use of vasopressor or inotropic medications prior to randomization.
- Intolerance/hypersensitivity to dipeptidyl peptidase-4 inhibitors.
- Patients expected to require intensive care unit admission or immediate surgical intervention.
- Participation in another trial assessing any treatment for COVID-19.
- Current treatment with a DPP-4 inhibitor.
- Pregnancy.
Sites / Locations
- Shamir Medical Center
- Rabin Medical Center, Beilinson Campus
- Rabin Medical Center, Hasharon Campus
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
DPP-4 inhibition
Control
Arm Description
Participants in the Dipeptidyl Peptidase-4 (DPP-4) inhibition group will receive linagliptin in addition to standard of care insulin regimen as per hospital protocol during their entire hospitalization.
Participants in the control group will receive only the standard of care insulin regimen as per hospital protocol during their entire hospitalization.
Outcomes
Primary Outcome Measures
Time to clinical change
Clinical change is defined as 2 points reduction in the World Health Organization (WHO) Ordinal Scale for Clinical Improvement of COVID-19: 0 - No clinical or virological evidence of infection; 1 - No limitation of activities; 2 - Limitation of activities; 3 - Hospitalized, no oxygen therapy; 4 - Oxygen by mask or nasal prongs; 5 - Non-invasive ventilation or high-flow oxygen; 6 - Intubation and mechanical ventilation; 7 - Ventilation + additional organ support - pressors, renal replacement therapy, extracorporeal membrane oxygenation; 8 - Death.
Secondary Outcome Measures
Percent of serious adverse events and premature discontinuation of treatment.
Percent of patients with clinical improvement.
Percent of patients with a 2 points reduction in the World Health Organization (WHO) Ordinal Scale for Clinical Improvement of COVID-19.
Length of hospitalization.
All-cause mortality.
Percent of supplemental oxygen use.
Supplemental oxygen-free days.
Percent of mechanical ventilation use.
Ventilator-free days.
Percent of ICU admissions.
ICU-free days.
Percent of 50% decrease in C-reactive protein (CRP) levels
Time to virologic response, defined as no detection of SARS-CoV-2 in a PCR test.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04371978
Brief Title
Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19
Official Title
Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Terminated
Why Stopped
End of COVID-19 outbreak in Israel
Study Start Date
October 1, 2020 (Actual)
Primary Completion Date
April 4, 2021 (Actual)
Study Completion Date
May 4, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rabin Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The coronavirus disease 2019 (COVID-19) is an emerging pandemic in 2020 caused by a novel coronavirus named SARS-CoV2. Diabetes confers a significant additional risk for COVID-19 patients. Dipeptidyl peptidase 4 (DPP-4) is a transmembrane glycoprotein expressed ubiquitously in many tissues. In addition to its effect on glucose levels, DPP-4 has various effects on the immune system and several diseases, including lung diseases. This trial aims to assess the safety and efficacy of linagliptin, a DPP-4 inhibitor, in the treatment of COVID-19. The trial will be randomized without blinding, with one are treated by insulin only for glucose balance and the other by insulin and linagliptin. The trial will assess the effects of linagliptin on different measures of COVID-19 recovery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID 19, Coronavirus, Diabetes Mellitus, Type 2, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Disease, Endocrine System Diseases, Dipeptidyl-Peptidase IV Inhibitors, Linagliptin, Severe Acute Respiratory Syndrome Coronavirus 2, Sars-CoV2, Hypoglycemic Agents, Respiratory Tract Diseases, Incretins, Hormones
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DPP-4 inhibition
Arm Type
Experimental
Arm Description
Participants in the Dipeptidyl Peptidase-4 (DPP-4) inhibition group will receive linagliptin in addition to standard of care insulin regimen as per hospital protocol during their entire hospitalization.
Arm Title
Control
Arm Type
No Intervention
Arm Description
Participants in the control group will receive only the standard of care insulin regimen as per hospital protocol during their entire hospitalization.
Intervention Type
Drug
Intervention Name(s)
Linagliptin 5 MG
Other Intervention Name(s)
Trajenta
Intervention Description
Linagliptin 5 mg PO once daily
Primary Outcome Measure Information:
Title
Time to clinical change
Description
Clinical change is defined as 2 points reduction in the World Health Organization (WHO) Ordinal Scale for Clinical Improvement of COVID-19: 0 - No clinical or virological evidence of infection; 1 - No limitation of activities; 2 - Limitation of activities; 3 - Hospitalized, no oxygen therapy; 4 - Oxygen by mask or nasal prongs; 5 - Non-invasive ventilation or high-flow oxygen; 6 - Intubation and mechanical ventilation; 7 - Ventilation + additional organ support - pressors, renal replacement therapy, extracorporeal membrane oxygenation; 8 - Death.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Percent of serious adverse events and premature discontinuation of treatment.
Time Frame
28 days
Title
Percent of patients with clinical improvement.
Description
Percent of patients with a 2 points reduction in the World Health Organization (WHO) Ordinal Scale for Clinical Improvement of COVID-19.
Time Frame
28 days
Title
Length of hospitalization.
Time Frame
28 days
Title
All-cause mortality.
Time Frame
28 days
Title
Percent of supplemental oxygen use.
Time Frame
28 days
Title
Supplemental oxygen-free days.
Time Frame
28 days
Title
Percent of mechanical ventilation use.
Time Frame
28 days
Title
Ventilator-free days.
Time Frame
28 days
Title
Percent of ICU admissions.
Time Frame
28 days
Title
ICU-free days.
Time Frame
28 days
Title
Percent of 50% decrease in C-reactive protein (CRP) levels
Time Frame
Up to 28 days
Title
Time to virologic response, defined as no detection of SARS-CoV-2 in a PCR test.
Time Frame
28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years.
History of or type 2 diabetes mellitus or a diagnosis of type 2 diabetes during hospitalization.
Confirmation of infection with SARS-CoV-2 by PCR testing.
Patients within 10 days from symptom onset or patients within 48 hours after laboratory diagnosis (SARS-CoV-2 PCR).
Exclusion Criteria:
WHO COVID-19 Ordinal Scale for Clinical Improvement ≥ 6.
Respiratory failure requiring mechanical ventilation prior to randomization.
Use of vasopressor or inotropic medications prior to randomization.
Intolerance/hypersensitivity to dipeptidyl peptidase-4 inhibitors.
Patients expected to require intensive care unit admission or immediate surgical intervention.
Participation in another trial assessing any treatment for COVID-19.
Current treatment with a DPP-4 inhibitor.
Pregnancy.
Facility Information:
Facility Name
Shamir Medical Center
City
Be'er Ya'aqov
Country
Israel
Facility Name
Rabin Medical Center, Beilinson Campus
City
Petah tikva
Country
Israel
Facility Name
Rabin Medical Center, Hasharon Campus
City
Petah tikva
Country
Israel
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35002970
Citation
Abuhasira R, Ayalon-Dangur I, Zaslavsky N, Koren R, Keller M, Dicker D, Grossman A. A Randomized Clinical Trial of Linagliptin vs. Standard of Care in Patients Hospitalized With Diabetes and COVID-19. Front Endocrinol (Lausanne). 2021 Dec 22;12:794382. doi: 10.3389/fendo.2021.794382. eCollection 2021.
Results Reference
derived
Learn more about this trial
Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19
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