COVID 19Phase 3NCT04371978
Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19
A Phase 3 study testing Linagliptin 5 MG in people with COVID 19 and Coronavirus, run by Rabin Medical Center at 3 sites in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID 19, Coronavirus, Diabetes Mellitus, Type 2
- What is being tested?
- Linagliptin 5 MG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 3 sitesIsrael
- Study dates
- 1 Oct 2020to 4 May 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
Israel3 sites
Shamir Medical Center
Be’er Ya‘aqov
Rabin Medical Center, Beilinson Campus
Petah Tikva
Rabin Medical Center, Hasharon Campus
Petah Tikva
About this study
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.
- Conditions
- COVID 19, Coronavirus, Diabetes Mellitus, Type 2, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Disease
- Being tested
- Linagliptin 5 MG
- Medical subject headings
- COVID-19, Coronavirus Infections, Diabetes Mellitus, Type 2, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Diseases, Endocrine System Diseases, Respiratory Tract Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Linagliptin 5 MGDrug
Also called Trajenta
Linagliptin 5 mg PO once daily
| Study group | Role | What they receive |
|---|---|---|
| DPP-4 inhibition | Experimental | 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. Receives: Drug: Linagliptin 5 MG |
| Control | No intervention | Participants in the control group will receive only the standard of care insulin regimen as per hospital protocol during their entire hospitalization. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
Secondary outcomes (12)
Percent of serious adverse events and premature discontinuation of treatment.
Measured: 28 days
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.
Measured: 28 days
Length of hospitalization.
Measured: 28 days
All-cause mortality.
Measured: 28 days
Percent of supplemental oxygen use.
Measured: 28 days
Supplemental oxygen-free days.
Measured: 28 days
Percent of mechanical ventilation use.
Measured: 28 days
Ventilator-free days.
Measured: 28 days
Percent of ICU admissions.
Measured: 28 days
ICU-free days.
Measured: 28 days
Percent of 50% decrease in C-reactive protein (CRP) levels
Measured: Up to 28 days
Time to virologic response, defined as no detection of SARS-CoV-2 in a PCR test.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2020
- Study start1 Oct 2020
- Primary completion4 Apr 2021
- Study completion4 May 2021
Why it stopped: End of COVID-19 outbreak in Israel
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID 19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rabin Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ran Abuhasira, Rabin Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04371978
- Sponsor's protocol ID
- 0303-20-RMC
- Status last verified
- May 2021
- First submitted
- 30 Apr 2020
- Last updated
- 2 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35002970
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19
- ClinicalTrials.gov ID
- NCT04371978
- Acronym / sponsor ID
- 0303-20-RMC
- Conditions
- COVID 19, Coronavirus, Diabetes Mellitus, Type 2, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: End of COVID-19 outbreak in Israel
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Rabin Medical CenterUniversity, hospital or other
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 4 Apr 2021 (actual)
- Study completion
- 4 May 2021 (actual)
- First posted
- 1 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DPP-4 inhibition | Experimental | Drug: Linagliptin 5 MGParticipants 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. |
| Control | No intervention | –Participants in the control group will receive only the standard of care insulin regimen as per hospital protocol during their entire hospitalization. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Linagliptin 5 MGAlso: TrajentaLinagliptin 5 mg PO once daily | Drug | DPP-4 inhibition |
Primary outcome
Time to clinical change
Time frame: 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.
12 secondary outcomes
Percent of serious adverse events and premature discontinuation of treatment.
Time frame: 28 days
Percent of patients with clinical improvement.
Time frame: 28 days
Length of hospitalization.
Time frame: 28 days
All-cause mortality.
Time frame: 28 days
Percent of supplemental oxygen use.
Time frame: 28 days
Supplemental oxygen-free days.
Time frame: 28 days
Percent of mechanical ventilation use.
Time frame: 28 days
Ventilator-free days.
Time frame: 28 days
Percent of ICU admissions.
Time frame: 28 days
ICU-free days.
Time frame: 28 days
Percent of 50% decrease in C-reactive protein (CRP) levels
Time frame: Up to 28 days
Time to virologic response, defined as no detection of SARS-CoV-2 in a PCR test.
Time frame: 28 days
Results and safety
The study was stopped early (reason given: End of COVID-19 outbreak in Israel). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2021.
- Derived from this study: PubMed 35002970Abuhasira 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Linagliptin 5 MG in people with COVID 19 and Coronavirus, run by Rabin Medical Center at 3 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: End of COVID-19 outbreak in Israel). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to clinical change (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04371978, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2021.