Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19

Sponsor

Rabin Medical Center (Other)

Overall Status

Terminated

CT.gov ID

NCT04371978

Collaborator

(none)

Enrollment

Locations

Arms

7.1

Actual Duration (Months)

21.3

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Linagliptin 5 MG	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

64 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19

Actual Study Start Date :

Oct 1, 2020

Actual Primary Completion Date :

Apr 4, 2021

Actual Study Completion Date :

May 4, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DPP-4 inhibition 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.	Drug: Linagliptin 5 MG Linagliptin 5 mg PO once daily Other Names: Trajenta
No Intervention: Control Participants in the control group will receive only the standard of care insulin regimen as per hospital protocol during their entire hospitalization.

Arm

Intervention/Treatment

Experimental: DPP-4 inhibition

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.

Drug: Linagliptin 5 MG

Linagliptin 5 mg PO once daily

Other Names:

Trajenta

No Intervention: Control

Participants in the control group will receive only the standard of care insulin regimen as per hospital protocol during their entire hospitalization.

Outcome Measures

Primary Outcome Measures

Time to clinical change [28 days]
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. [28 days]
Percent of patients with clinical improvement. [28 days]
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. [28 days]
All-cause mortality. [28 days]
Percent of supplemental oxygen use. [28 days]
Supplemental oxygen-free days. [28 days]
Percent of mechanical ventilation use. [28 days]
Ventilator-free days. [28 days]
Percent of ICU admissions. [28 days]
ICU-free days. [28 days]
Percent of 50% decrease in C-reactive protein (CRP) levels [Up to 28 days]
Time to virologic response, defined as no detection of SARS-CoV-2 in a PCR test. [28 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country
1	Shamir Medical Center	Be'er Ya'aqov	Israel
2	Rabin Medical Center, Beilinson Campus	Petah tikva	Israel
3	Rabin Medical Center, Hasharon Campus	Petah tikva	Israel