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

Phase 3

Terminated

• Conditions: Metabolic Disease; Endocrine System Diseases; COVID 19; Coronavirus; Diabetes Mellitus, Type 2; Diabetes Mellitus; Dipeptidyl-Peptidase IV Inhibitors; Linagliptin; Severe Acute Respiratory Syndrome Coronavirus 2; Sars-CoV2
• Interventions: Drug: Linagliptin 5 MG

• Registration Number: NCT04371978
• Lead Sponsor: Rabin Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-04-30
• Study First Submitted QC: 2020-04-30
• Study First Posted: 2020-05-01
• Study Start: 2020-10-01
• Primary Completion: 2021-04-04
• Status Verified: 2021-05
• Study Completion: 2021-05-04
• Last Update Submitted: 2021-05-28
• Last Update Posted: 2021-06-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 64

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DPP-4 inhibition	Linagliptin 5 MG	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Percent of serious adverse events and premature discontinuation of treatment.	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

Trial Locations

Locations (3)

Shamir Medical Center; 🇮🇱 Be'er Ya'aqov, Israel

Rabin Medical Center, Hasharon Campus; 🇮🇱 Petah tikva, Israel

Rabin Medical Center, Beilinson Campus; 🇮🇱 Petah tikva, Israel