Sitagliptin Treatment in Diabetic COVID-19 Positive Patients

NCT ID: NCT04382794

Last Updated: 2020-07-09

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 338 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-05-14
• Study Completion Date: 2020-06-15

Brief Summary

Coronavirus Pathology is frequently associated with both diabetes mellitus and metabolic syndrome. In particular, results of observational studies and meta-analyzes configure diabetes as one of the main risk factors for the development of complications and unfavorable course of SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome), the syndromes caused respectively by SARS- VOC coronavirus and MERS-COV coronavirus. The available data confirm this association also in the clinical picture of the infection supported by SARS-COV 2 (COVID-19). In the epidemic outbreak that erupted at the beginning of 2020 in the Lombardy Region, about two thirds of the patients who died from COVID-19 were affected by diabetes mellitus. COVID-19 occurs in 70% of cases with an inflammatory pathology of the airways that can be fed by a cytokine storm and result in severe respiratory failure (10% cases) and death (5%). At the moment, the mainly involved pathophysiological molecular mechanisms are not clearly defined. It has been hypothesized that the transmembrane glycoprotein type II CD26, known for the enzyme activity Dipeptilpeptidase 4 exerted by its extracellular domain, may play a fundamental role in this process. In addition, it is considerably expressed at the parenchyma and lung interstitium level and carries out both systemic and paracrine enzymatic activity, modulating the activity of various proinflammatory cytokines, growth factors and vasoactive peptides at the level of the deep respiratory tract. The pulmonary parenchyma and the interstitium express significantly the Dipeptilpeptidase 4 protein, which in the Middle East Respiratory Syndrome favors the entry of the virus into the cells, thus allowing the virus to replicate within the cells and thus spread throughout the cell inside the organism. Dipeptilpeptidase 4 regulates the function of bioactive peptides and above all of cytokines, vasoactive peptides and chemokines present at the level of the mesothelium, of the deep respiratory tract (alveolar epithelium and alveolar bronchus), of endothelial and immune cells triggering the inflammatory storm. In line with this evidence, it has been hypothesized that acute respiratory disease from Coronavirus may depend on the massive localization of Dipeptilpeptidase 4 in lung tissue. Furthermore, the involvement of Dipeptilpeptidase 4 in other chronic respiratory diseases has been demonstrated. Starting from these observations we hypothesized that the selective blockade of Dipeptilpeptidase 4 can favorably modulate the pulmonary inflammatory response in the subject affected by COVID-19. Among the drugs that selectively block Dipeptilpeptidase 4, the one with greater affinity precisely for Dipeptilpeptidase 4 is Sitagliptin.

Detailed Description

An observational, retrospective-case control, multi-center study is proposed to evaluate any effects of Sitagliptin on clinical, laboratory and instrumental parameters in the course of hospitalization for COVID-19. The data will be extracted anonymously from the computerized medical records commonly used in clinical practice by the centers involved in the study. The evaluation will be performed by comparing the parameters of COVID-19 positive diabetic patients treated with Sitagliptin with those of a group of COVID-19 positive diabetic patients not treated with Sitagliptin. All diabetic subjects treated with Sitagliptin (100 mg / day, 50 mg / day or 25 mg / day) and all diabetic subjects not treated with Sitagliptin, eligible for inclusion / exclusion criteria, will be included in the analysis.

The clinical data of patients that will be collected anonymously during hospitalization will include: smoking habit, remote medical history aimed at assessing the presence of comorbidities (atrial fibrillation, heart failure, hypertension, arterial hypertension, chronic obstructive pulmonary disease, other lung disease, chronic renal failure, decay cognitive, Parkinson's disease, autoimmune diseases), pharmacological history (treatment introduced during hospitalization for COVID-19, respiratory failure or other complications; use of ACE-inhibitors, sartans, calcium channel blockers, diuretics, antiarrhythmics, beta blockers, anti-aggregants, anticoagulants, neuroleptics ). Anthropometric parameters including blood pressure measurement and BMI will also be collected.

For all patients, the following data will be collected at the baseline (first data available upon entry into the hospitalization regime) and upon discharge:

• Clinical picture and symptoms (presence of cough, body temperature, respiratory rate, need for ventilatory support, duration of ventilatory support in days, duration of oxygen therapy in day, duration of hospitalization in Intensive Care Unit in days, total length of stay in days, blood gas parameters, PaO2 / FiO2 ratio, oxygen saturation by pulse oximeter)
• Routine blood chemistry tests performed in hospitalization (e.g. glycemia, reactive protein C, blood count with formula, erythrocyte sedimentation rate, blood gas analysis, LDH, inflammation indices).
• Instrumental exams (chest x-ray)
• glycated hemoglobin
• Serum creatinine and Estimated Glomerular Filtration Rate (estimated with CKD-EPI)
• Presence of specific comorbidities for diabetes
• Average daily blood sugar levels (from capillary blood)

Conditions

Covid19

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

DMT2 COVID19 positive patients treated with Sitagliptin

The anonymous data relating to the clinical, laboratory and instrumental parameters of patients hospitalized for COVID-19 and suffering from type 2 diabetes treated with Sitagliptin will be extracted from the medical records currently in use in the centers participating in the study. The data will be anonymous and not attributable to individual subjects

Retrospective case-control analysis

Intervention Type: DRUG

Evaluation of clinical, laboratory and instrumental parameters of diabetic patients during hospitalization for COVID-19. The data will be extracted anonymously from the computerized medical records commonly used in clinical practice by the centers involved in the study

DMT2 COVID19 positive patients not treated with Sitagliptin

The anonymous data relating to the clinical, laboratory and instrumental parameters of patients hospitalized for COVID-19 and suffering from type 2 diabetes not treated with Sitagliptin will be extracted from the medical records currently in use in the centers participating in the study. The data will be anonymous and not attributable to individual subjects

Retrospective case-control analysis

Intervention Type: DRUG

Evaluation of clinical, laboratory and instrumental parameters of diabetic patients during hospitalization for COVID-19. The data will be extracted anonymously from the computerized medical records commonly used in clinical practice by the centers involved in the study

Interventions

Retrospective case-control analysis

Evaluation of clinical, laboratory and instrumental parameters of diabetic patients during hospitalization for COVID-19. The data will be extracted anonymously from the computerized medical records commonly used in clinical practice by the centers involved in the study

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of type 2 diabetes, according to ADA 2020 criteria
• Diagnosis of COVID-19 (positive SARS-COV2 RNA buffer) with pneumonia, with or without an increase in inflammation indexes, with or without respiratory failure

Exclusion Criteria

• Pregnancy
• Type 1 diabetes
• Presence of other acute infections in place
• Presence of serious diseases or conditions that make the patient unsuitable for the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Papa Giovanni XXIII Hospital

OTHER

Sponsor Role: collaborator

Fondazione IRCCS Policlinico San Matteo di Pavia

OTHER

Sponsor Role: collaborator

Humanitas Hospital, Italy

OTHER

Sponsor Role: collaborator

Ospedale dell'Angelo, Venezia-Mestre

OTHER

Sponsor Role: collaborator

University of Pavia

OTHER

Sponsor Role: collaborator

University of Milan

OTHER

Sponsor Role: lead

Responsible Party

Paolo Fiorina, MD

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paolo Fiorina, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

ASST FBF Sacco

Locations

ASST FBF-Sacco P.O. Sacco

Milan, MI, Italy

Papa Giovanni XXIII Hospital

Bergamo, , Italy

Ospedale dell'Angelo, Venezia-Mestre

Mestre, , Italy

Humanitas Hospital

Milan, , Italy

University of Pavia

Pavia, , Italy

IRCCS Policlinico S. Matteo

Pavia, , Italy

Countries

Italy

References

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Reference Type: BACKGROUND

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Other Identifiers

5/2020

Identifier Type: -

Identifier Source: org_study_id