Dapagliflozin in Type 2 Diabetes Patients, a Retrospective Cohort Study From Turkey (DAPA-TURK)

Dapagliflozin in Type 2 Diabetes Patients in Routine Internal Medicine and Endocrinology Outpatient Clinical Care; a Retrospective Cohort Study From Turkey

Background/Rationale:

Objectives and Hypotheses: To describe characteristics of patients with type 2 diabetes (T2D) prescribed dapagliflozin in routine internal medicine and endocrinology outpatient clinical care in Turkey; to describe changes in HbA1c(%), weight(kg), BMI(kg/m^2) and blood pressure (BP)(mmHg) in these patients; and the discontinuation rates of dapagliflozin in the first 6 months of treatment.

Methods:

Study design: a retrospective observational cohort study. Data Source(s): Patient medical records of 81 different centres. Study Population: patients with a diagnosis of T2D, a first prescription for dapagliflozin, between July 2016 and Aug 2017 and who have been registered in the participating centre at least 6 months prior to first prescription of dapagliflozin.

Study variables: patient characteristics: age, gender, smoking status, co-morbidities, duration of diabetes, prescribed medicines, HbA1c(%), weight(kg), body mass index (BMI)(kg/m^2) and blood pressure (BP)(mmHg).

Outcome(s): description of patient characteristics, HbA1c(%), weight(kg), BMI(kg/m^2) and BP(mmHg) at baseline and during use of dapagliflozin at first visit (2,3 or 4 months) and second visit (5 or 6 months).

Sample Size Estimations:1500 patients Statistical Analysis: the baseline characteristics and follow up variables will be described using frequency and percentage distributions for categorical variables. Continuous and count variables will be described using mean (± standard deviation), median (quartiles) and 95% confidence intervals. Proportion of patients falling above/below certain weight(kg)/BMI(kg/m^2), HbA1c(%) and BP(mmHg) thresholds will be derived. HbA1c(%), weight(kg), BMI(kg/m^2) and BP(mmHg) will be described at baseline and during use of dapagliflozin. Over all questionnaire response rate and rate of response to reasons for prescribing dapagliflozin will be described.

Limitations: Variation in timing and completeness of clinical measures. The patient medical records are not collected for research purposes and the diagnostic and procedure coding on such data may be recorded incorrectly or not recorded at all, thereby potentially introducing measurement error with respect to code-based variables. The centres participating in the study, record that a prescription was issued, but not whether it was dispensed from the pharmacy.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Forxiga

Detailed Description

This study is a descriptive retrospective observational cohort study using data from Turkish patient medical records from 81 different internal medicine and/or endocrinology clinics across the whole country.

The study cohort will include T2D patients who received at least one prescription for dapagliflozin for the first time between July 2016 and Aug 2017 and who have been registered in that centre for at least 6 months prior to the first dapagliflozin prescription.

The selection of sites and investigators will be made with an aim to achieve representativeness of the way dapagliflozin treated T2D patients are managed across Turkey. The National Coordinator will provide advice regarding the proportion of the different types of centres (Internal medicine, endocrinology clinics, different types of hospitals, geographical distribution) and investigators (different types of specialists) involved in dapagliflozin treated T2D patient management. The National Coordinator will also provide insight on the national situation regarding dapagliflozin medication prescription (reimbursement, public or private insurance). All this information will be used to select sites and investigators for the study, resembling as closely as possible, the real-world situation.

Sites will also be evaluated for existence and use of electronic medical records as part of feasibility. Data quality of sites will be assessed before initiation visit. The study centre database should provide at least 20 patients to the study. In case the study centre, can provide more than 20 patients, then patients will be selected randomly by the Contract Research Organization. Contract Research Organization will also record total number of eligible patients, their age and sex details before performing randomization. The randomization process will be performed at the study site after initiation visit by Contract Research Organization. The investigator of the centre will enter only selected patients to study Case Report Form. The Contract Research Organization will also perform 100% source document verification following completion of Case Report Forms by the investigator. All centres will be evaluated by Contract Research Organization at initiation visit in terms of data quality (Baseline, first visit and second visit data of eligible patients)

The date of the first prescription for dapagliflozin in patient medical records is the index date. Patients will be followed from the index date until the earliest of transfer out date, death date or end date of patient records (last date of data collection). Required data mentioned in baseline characteristics (section 5.1) will be recorded at index date, first visit (2 or 3 or 4 months after index date) and second visit (5 or 6 months after index date) of treatment (section 5.2).

Dataset quality will be assessed by Contract Research Organization at initiation visit. Site investigator is responsible for entering data to Case Report Forms. Paper based Case Report Form system will be used for this study. Datasets can differ for each hospital and patient's records can be electronic and/or printed. The investigator will collect all necessary data for each patient retrospectively from the most reliable data source in the clinic. All collected data will be verified by the Contract Research Organization.

• Study Type: Observational
• Enrollment (Actual): 1683

Contacts and Locations

Study Locations

• Turkey
  • Ankara, Turkey, 06280
    • Keçiören Training and Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study cohort will be selected from patient records of 81 different centres. 1500 patients are planned to include in this study.

Description

Inclusion Criteria:

• Age ≥18 and ≤75 years at index date.
• First prescription for dapagliflozin between July 2016 and Aug 2017
• Minimum 6 months of registration in the centres at the index date
• Established Type 2 diabetes prior to the index date

Exclusion Criteria:

• Patients with Type 1 diabetes
• Patients with gestational diabetes
• Being included in another interventional clinical trial at between index date and enrollment date
• Estimated Glomerular Filtration Rate < 30 ml/min

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c(%)	To record the mean change in HbA1C from baseline [ Time Frame: 6 Months ] Changes over time (6 months) in HbA1c(%) value in these patients.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in Total body weight [ Time Frame: 6 Months ]	The mean changes from mean baselines and at Month 6 in Total body weight.	6 months
Changes from baseline in BMI [ Time Frame: 6 Months ]	The mean changes from mean baselines and at Month 6 in BMI	6 months
Changes from baseline in Systolic Blood Pressures	The mean changes from mean baselines and at Month 6 in Systolic Blood Pressures	6 months
Changes from baseline in Diastolic Blood Pressures [ Time Frame: 6 Months ]	The mean changes from mean baselines and at Month 6 in Diastolic Blood Pressures	6 months
Discontinuation rates of dapagliflozin in the first 6 months of treatment	Discontinuation rates of dapagliflozin in the first 6 months of treatment	6 months

Collaborators and Investigators

• Sponsor: AstraZeneca Turkey
• Collaborators: Optimum Contract Research Organization, Turkey
• Investigators: Principal Investigator: Süleyman Özçaylak, Spec.Dr., Diyarbakır Gazi Yaşargil T&R Hospital; Principal Investigator: Kürşat Dal, Assc.ProfDr, Keçiören T&R Hospital; Principal Investigator: Muhammed Mu Demirpençe, Spec. Dr., Tepecik T&R Hospital; Principal Investigator: Erdal Kan, Spec.Dr., Samsun Medicana Hospital; Principal Investigator: Tuğba Arkan, Spec. Dr., Kocaeli Derince T&R Hospital; Principal Investigator: Canan Ersoy, Prof.Dr., Uludag University; Principal Investigator: Mustafa Araz, Prof.Dr., University of Gaziantep; Principal Investigator: Okan Bakıner, Assc.ProfDr, Adana Başkent University; Principal Investigator: Ramazan Kaya, Spec.Dr., Mersin Tarsus State Hospital; Principal Investigator: Eren Gürkan, Ast.Prof.Dr., Mustafa Kemal University; Principal Investigator: Hayati Ayakta, Spec.Dr., Manisa Private Grand Hospital; Principal Investigator: Pınar Sırmatel, Spec.Dr., Edirne State Hospital; Principal Investigator: Berna Da Ekiz, Spec.Dr., Muğla Private İzan Hospital; Principal Investigator: Faruk Kılınç, Spec.Dr., Firat University; Principal Investigator: İbrahim Şahin, Prof.Dr., Inonu University; Principal Investigator: Rıfkı Üçler, Asc.Prof.Dr, Van 100.Yıl University; Principal Investigator: Semin M Fenkçi, Prof.Dr., Pamukkale University; Principal Investigator: Mustafa Aydemir, Spec.Dr., Afyon State Hospital; Principal Investigator: Emre Çiçekli, Spec.Dr., Sivas Medicana Hospital; Principal Investigator: Şahin Doğanay, Spec.Dr, Yenimahalle T&R Hospital; Principal Investigator: Özgür Keşkek, Asc.Prof.Dr., Adana City Hospital; Principal Investigator: Aytekin Oğuz, Prof.Dr., MEDENIYET UNIVERSITY; Principal Investigator: Kerem Sezer, Prof.Dr., Mersin University; Principal Investigator: Oğuzhan S Dizdar, Spec.Dr., Kayseri T&R Hospital; Principal Investigator: Yasin Kocaöz, Spec.Dr., Menemen State Hospital; Principal Investigator: Mahir Cengiz, Spec.Dr., Istanbul University Cerrahpasa Medical Faculty; Principal Investigator: Nilgün G Gıynaş, Spec.Dr., Ankara T&R Hospital; Principal Investigator: Hakan Doğan, Spec.Dr., Bozyaka T&R Hospital; Principal Investigator: Erdal Gündoğan, Spec.Dr., Bağcılar T&R Hospital; Principal Investigator: Çağlar Köseoğlu, Spec.Dr., Gölbaşı State Hospital; Principal Investigator: Rıfat Bozkuş, Spec.Dr., Ulus State Hospital; Principal Investigator: Murat Medeni, Spec.Dr., Bornova Türkan Özilhan State Hospital; Principal Investigator: Mehmet Çelebioğlu, Spec.Dr., Eskişehir Private Anadolu Hospital; Principal Investigator: Mustafa Çalışkan, Spec.Dr., Düzce State Hospital; Principal Investigator: Metin Güçlü, Asc.Prof.Dr., Bursa Yüksek İhtisas T&R Hospital; Principal Investigator: Özcan Özbağ, Spec.Dr., Gaziantep T&R Hospital; Principal Investigator: Taner Bayraktaroğlu, Prof.Dr., Bulent Ecevit University; Principal Investigator: Ömür Tabak, Asc.Prof.Dr., Kanuni Sultan Süleyman T&R Hospital; Principal Investigator: Erhan Bozkurt, Spec.Dr., Emirdağ State Hospital; Principal Investigator: Selçuk Sezikli, Spec.Dr., Merzifon State Hospital; Principal Investigator: Ersen Karakılıç, Spec.Dr., Canakkale State Hospital; Principal Investigator: Ayça S Erdem, Spec.Dr., Uskudar State Hospital; Principal Investigator: Deniz Gezer, Spec.Dr., Mersin City State Hospital; Principal Investigator: Nuh Baklacı, Spec.Dr., Hatay Akademi Hospital; Principal Investigator: Sabriye Ö Kafesçiler, Spec.Dr., Manisa State Hospital; Principal Investigator: Sayid S Zuhur, Asc.Prof.Dr., Namik Kemal University; Principal Investigator: Göktürk Kılınç, Spec.Dr., Fethiye State Hospital; Principal Investigator: Mustafa Timurkağan, Spec.Dr., Elazığ T&R Hospital; Principal Investigator: Ümit Çınkır, Spec.Dr., Gaziantep Medicalpark Hospital; Principal Investigator: Semra Tursun, Spec.Dr., Denizli Private Tekden Hospital; Principal Investigator: Memnune S Ulu, Asc.Prof.Dr., Afyon Kocatepe University; Principal Investigator: Çiğdem B Tuna, Spec.Dr., Tokat State Hospital; Principal Investigator: Harun Aysal, Spec.Dr., Antalya Ataturk State Hospital; Principal Investigator: Züleyha Karaca, Asc.Prof.Dr., TC Erciyes University; Principal Investigator: Murat Akbaş, Spec.Dr., İstanbul Eyüp State Hospital; Principal Investigator: Ahmet Z Şahin, Spec.Dr., Adana Aşkım Tüfekçi State Hospital; Principal Investigator: Esra Çil Şen, Spec.Dr., Şişli Etfal T&R Hospital; Principal Investigator: Mehmet Çelik, Spec.Dr., Antalya T&R Hospital; Principal Investigator: Metin Sarıkaya, Spec.Dr., Antalya T&R Hospital; Principal Investigator: Hacı Bayram, Spec.Dr., Ümraniye T&R Hospital; Principal Investigator: Alparslan K Tuzcu, Prof.Dr., Dicle University; Principal Investigator: Derun T Ertuğrul, Asc.Prof.Dr., Keçiören T&R Hospital; Principal Investigator: İlhan Yetkin, Prof.Dr., Gazi University; Principal Investigator: Mehmet Çoşkun, Spec.Dr., Diyarbakır Gazi Yaşargil T&R Hospital; Principal Investigator: Kevser Onbaşı, Prof.Dr., T.C. Dumlupınar Üniversitesi; Principal Investigator: Mehmet A Eren, Asc.Prof.Dr., Harran University; Principal Investigator: Rıfat Emral, Prof.Dr., Ankara University; Principal Investigator: Ramazan Gen, Asc.Prof.Dr., Mersin University; Principal Investigator: Esra Ataoğlu, Asc.Prof.Dr., Haseki T&R Hospital; Principal Investigator: Barış Akıncı, Prof.Dr., Dokuz Eylul University; Principal Investigator: Ramazan Sarı, Prof.Dr., Akdeniz University; Principal Investigator: Emre Bozkırlı, Asc.Prof.Dr., Adana Başkent University; Principal Investigator: Kubilay Karşıdağ, Prof.Dr., Istanbul University Istanbul Medical Faculty; Principal Investigator: Tamer Tetiker, Prof.Dr., Cukurova University; Principal Investigator: Levent Kebapçılar, Prof.Dr., Selcuk University; Principal Investigator: Yıldız Okuturlar, Asc.Prof.Dr., Bakırköy Dr.Sadi Konuk T&R Hospital; Principal Investigator: Enver Şükrü Göncüoğlu, Spec.Dr., Dr. Nazif Bağrıaçık Kadıköy Hospital; Principal Investigator: Bengür Taşkıran, Spec.Dr., Eskişehir Yunus Emre State Hospital; Principal Investigator: İnan Anaforoğlu, Asc.Prof.Dr., Trabzon Medicalpark Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 24, 2017
• Primary Completion (ACTUAL): December 31, 2017
• Study Completion (ACTUAL): February 28, 2018

Study Registration Dates

• First Submitted: December 4, 2017
• First Submitted That Met QC Criteria: January 22, 2018
• First Posted (ACTUAL): January 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 7, 2018
• Last Update Submitted That Met QC Criteria: March 6, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Diabetes; HbA1c; Dapagliflozin; BP; Endocrinology; BMI; Type II diabetes mellitus; Internal diseases
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: AZTRMT 2017-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No