Clinical trial NCT04371978: 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
Overall status: TERMINATED
Phase: PHASE3
Conditions: 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
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
First posted: 2020-05-01
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years.
2. History of or type 2 diabetes mellitus or a diagnosis of type 2 diabetes during hospitalization.
3. Confirmation of infection with SARS-CoV-2 by PCR testing.
4. Patients within 10 days from symptom onset or patients within 48 hours after laboratory diagnosis (SARS-CoV-2 PCR).

Exclusion Criteria:

1. WHO COVID-19 Ordinal Scale for Clinical Improvement ≥ 6.
2. Respiratory failure requiring mechanical ventilation prior to randomization.
3. Use of vasopressor or inotropic medications prior to randomization.
4. Intolerance/hypersensitivity to dipeptidyl peptidase-4 inhibitors.
5. Patients expected to require intensive care unit admission or immediate surgical intervention.
6. Participation in another trial assessing any treatment for COVID-19.
7. Current treatment with a DPP-4 inhibitor.
8. Pregnancy.

Primary outcomes:
measure: Time to clinical change
timeFrame: 28 days
Secondary outcomes:
measure: Percent of serious adverse events and premature discontinuation of treatment.
timeFrame: 28 days
measure: Percent of patients with clinical improvement.
timeFrame: 28 days
measure: Length of hospitalization.
timeFrame: 28 days
measure: All-cause mortality.
timeFrame: 28 days
measure: Percent of supplemental oxygen use.
timeFrame: 28 days
measure: Supplemental oxygen-free days.
timeFrame: 28 days
measure: Percent of mechanical ventilation use.
timeFrame: 28 days
measure: Ventilator-free days.
timeFrame: 28 days
measure: Percent of ICU admissions.
timeFrame: 28 days
measure: ICU-free days.
timeFrame: 28 days
measure: Percent of 50% decrease in C-reactive protein (CRP) levels
timeFrame: Up to 28 days
measure: Time to virologic response, defined as no detection of SARS-CoV-2 in a PCR test.
timeFrame: 28 days
Other outcomes:
Locations:
city: Be'er Ya'aqov
country: Israel
facility: Shamir Medical Center
city: Petah tikva
country: Israel
facility: Rabin Medical Center, Beilinson Campus
city: Petah tikva
country: Israel
facility: Rabin Medical Center, Hasharon Campus
Study officials:
References:
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.