Diabetes Mellitus Type 2Phase 4DAPACARDNCT03387683
A Clinical Study to Investigate the Effects of Dapagliflozin on Heart Work, Heart Nutrient Uptake, and Heart Muscle Efficiency in Type 2 Diabetes Patients
A Phase 4 study testing dapagliflozin in people with Diabetes Mellitus Type 2, run by AstraZeneca at 2 sites in 2 countries.
Trial summary
This is a randomised, placebo-controlled, double-blind, parallel-group, international, multicentre, Phase IV study to investigate the effects of dapagliflozin on cardiac substrate uptake, myocardial efficiency and myocardial contractile work in T2D patients. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Diabetes Mellitus Type 2
- What is being tested?
- dapagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 28 Feb 2018to 19 Mar 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
- Females or males ≥40 years up to 75 years of age.
- Individuals with type 2 diabetes diagnosed for at least 6 months based on the American Diabetes Association standards (ADA, 2017) and on stable dose of metformin for at least 6 weeks prior to screening and HbA1c at screening visit of ≥42 mmol/mol (6.0%) and ≤75 mmol/mol (9.0%) measured at local hospital laboratory.
- No significant signs or symptoms of coronary artery disease or, if known coronary artery disease, currently free of symptoms and a) all major epicardial vessels with <50% stenosis within 12 months prior to screening, or b) if revascularized with all major epicardial vessels with <50% remaining stenosis after stenting or bypass surgery procedure determined between 3 and 12 months prior to screening.
- Normal left ventricular ejection fraction (≥50%) assessed within 1 year prior to informed consent, and if applicable, after most recent acute episode of coronary artery syndrome, or at screening visit.
- Body mass index (BMI) ≥ 25 kg/m2.
Who cannot join
- Blood pressure at screening that would require a change in blood pressure treatment over the study period or any of the following: systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg.
- History of stroke or other clinically significant cerebrovascular disease.
- Any of the following cardiovascular diseases known within 3 months prior to signing the consent at enrolment:
- Atrial fibrillation, or other unstable or severe arrhythmia affecting heart function
- Unstable heart failure or any heart failure with NYHA class III and IV
- Significant valvular disease
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- Significant peripheral artery disease
- Planned cardiac surgery or angioplasty within 3 months from enrolment.
- Clinical diagnosis of type 1 diabetes, maturity onset diabetes of the young (MODY), secondary diabetes or diabetes insipidus.
- Verified body weight variability of >3 kg during the 3 proceeding months before screening.
- Active malignancy requiring treatment at the time of visit 1 (with the exception of successfully treated basal cell or treated squamous cell carcinoma).
- Patients with severe hepatic impairment (Child-Pugh class C).
- Unstable or rapidly progressing renal disease.
- Clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- Ongoing treatment with other antidiabetic drugs than metformin.
- Ongoing treatment with loop diuretics.
- Ongoing weight-loss diet (hypocaloric diet) or use of weight loss agents.
- Contraindications to dapagliflozin therapy.
- Ongoing treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except for T2D.
- Previous enrolment in the present study or participation in another clinical study with an investigational product during the last 1 month prior to screening.
- Estimated Glomerular Filtration Rate (eGFR) <45 mL/min/1.73 m2.
- Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study treatment intake.
- Any condition when MRI and CT-PET is contraindicated such as, but not limited to, having a metallic implant (such as pacemaker or cochlear implant), permanent make up, claustrophobia or BMI ≥40 kg/m2).
- Involvement in the planning and/or conduct of the study.
- Plasma donation within one month of screening or any blood donation/blood loss >450 mL during the 3 months prior to screening.
- Women who has a positive pregnancy test at enrolment or randomization, or are breastfeeding.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Double-blind, Randomized, Parallel Group, Phase IV Study to Investigate the Effects of DAPAgliflozin on CARDiac Substrate Uptake, Myocardial Efficiency and Myocardial Contractile Work in Type 2 Diabetes Patients
This is a randomised, placebo-controlled, double-blind, parallel-group, international, multicentre, Phase IV study to investigate the effects of dapagliflozin on cardiac substrate uptake, myocardial efficiency and myocardial contractile work in T2D patients. Eligible subjects with T2D before randomisation and fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomised in a 1:1 ratio to dapagliflozin 10 mg or placebo once daily and treated for six weeks. The study includes five visits.
Read the detailed description
The following will be assessed at Baseline and at the end of the treatment period;
- MRI scanning in order to assess cardiac function and morphology. The MRI scanning will be made after fasting for at least 6 hours in the same time of day at all visits. The cardiac MRI examination will be performed in accordance with a pre-defined MRI protocol, with the total scan time at each visit estimated to 45 minutes. Images from all sites will be analyzed centrally at the core-lab using a dedicated software package and certified analysts.
- CT-PET scanning will be made to assess myocardial function and metabolism, as well as fatty acid metabolism in brain, liver and kidney cortex. The CT-PET scanning will be made after a fast as well as abstinence from nicotine, alcohol and caffeine for at least 6 hours at the same time of day at all visits.
- A cardiac 11C-Acetate PET/CT examination is performed (IV 400 MBq 11C-Acetate).
- A cardiac 18F-FTHA PET/CT examination is performed (IV 150 MBq 18F-FTHA). The subject is further examined by PET/CT over the liver, kidney cortex and brain (in this order) for uptake of 18F-FTHA. Arterialized venous samples are acquired throughout to assess P-NEFA and 18F-FTHA metabolism by metabolite analysis
- Conditions
- Diabetes Mellitus Type 2
- Being tested
- dapagliflozin, placebo
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dapagliflozinDrug
Also called Forxiga 10mg
dapagliflozin 10mg
placeboDrug
placebo to match dapagliflozin
| Study group | Role | What they receive |
|---|---|---|
| placebo | Placebo comparator | placebo tablets once daily Receives: Drug: placebo |
| dapagliflozin 10mg | Experimental | dapagliflozin 10mg tablets once daily Receives: Drug: dapagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adjusted Mean Change From Baseline in Global Longitudinal Strain of the Left Ventricle (GLSLV) at End of Treatment.
Patients underwent magnetic resonance imaging (MRI) examination to determine the GLSLV, which is expressed as a percentage. The least square mean (LSM) change from baseline estimates were generated from an analysis of covariance (ANCOVA) model with treatment and baseline value of the endpoint as covariates.
Measured: Baseline (Day 1) and end of treatment (Day 42)
Secondary outcomes (1)
Adjusted Mean Change From Baseline in Myocardial Efficiency at End of Treatment.
A clinical radiologic assessment of acquired computed tomography and positron emission tomography (CTPET)-[11C]-acetate images was performed to determine myocardial efficiency. The myocardial efficiency calculation was based on an estimate of energy used for producing LV contractile work (mean arterial pressure (MAP) x stroke volume (SV) x heart rate (HR) / myocardial mass) compared to the total cardiac work (calculated based on the total myocardial oxygen consumption per myocardial mass) and is expressed as a percentage. The LSM change from baseline estimates, were generated from an ANCOVA model with treatment and baseline value of the endpoint as covariates.
Measured: Baseline (Day 1) and end of treatment (Day 42)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2018
- Study start28 Feb 2018
- Primary completion19 Mar 2019
- Study completion19 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetes Mellitus Type 2Studies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jonas Oldgren, MD, PhD, Principal investigator, Uppsala Clinical Research Center, Upppsala SwedenPirjo Nuutila, MD, PhD, Principal investigator, University of Turku, Turku, Finland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03387683
- Sponsor's protocol ID
- D1690C00063
- Other IDs
- 2017-003820-58, 2017
- Acronym
- DAPACARD
- Status last verified
- Apr 2020
- First submitted
- 18 Dec 2017
- Last updated
- 27 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Parallel Group, Phase IV Study to Investigate the Effects of DAPAgliflozin on CARDiac Substrate Uptake, Myocardial Efficiency and Myocardial Contractile Work in Type 2 Diabetes Patients
- ClinicalTrials.gov ID
- NCT03387683
- Acronym / sponsor ID
- DAPACARD / D1690C00063
- Conditions
- Diabetes Mellitus Type 2
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 28 Feb 2018 (actual)
- Primary completion
- 19 Mar 2019 (actual)
- Study completion
- 19 Mar 2019 (actual)
- First posted
- 2 Jan 2018 (actual)
- Results
- Posted 25 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomised, placebo-controlled, double-blind, parallel-group, international, multicentre, Phase IV study to investigate the effects of dapagliflozin on cardiac substrate uptake, myocardial efficiency and myocardial contractile work in T2D patients. Eligible subjects with T2D before randomisation and fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomised in a 1:1 ratio to dapagliflozin 10 mg or placebo once daily and treated for six weeks. The study includes five visits.
Detailed description
The following will be assessed at Baseline and at the end of the treatment period;
- MRI scanning in order to assess cardiac function and morphology. The MRI scanning will be made after fasting for at least 6 hours in the same time of day at all visits. The cardiac MRI examination will be performed in accordance with a pre-defined MRI protocol, with the total scan time at each visit estimated to 45 minutes. Images from all sites will be analyzed centrally at the core-lab using a dedicated software package and certified analysts.
- CT-PET scanning will be made to assess myocardial function and metabolism, as well as fatty acid metabolism in brain, liver and kidney cortex. The CT-PET scanning will be made after a fast as well as abstinence from nicotine, alcohol and caffeine for at least 6 hours at the same time of day at all visits.
- A cardiac 11C-Acetate PET/CT examination is performed (IV 400 MBq 11C-Acetate).
- A cardiac 18F-FTHA PET/CT examination is performed (IV 150 MBq 18F-FTHA). The subject is further examined by PET/CT over the liver, kidney cortex and brain (in this order) for uptake of 18F-FTHA. Arterialized venous samples are acquired throughout to assess P-NEFA and 18F-FTHA metabolism by metabolite analysis
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| placebo | Placebo comparator | Drug: placeboplacebo tablets once daily |
| dapagliflozin 10mg | Experimental | Drug: dapagliflozindapagliflozin 10mg tablets once daily |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
- Females or males ≥40 years up to 75 years of age.
- Individuals with type 2 diabetes diagnosed for at least 6 months based on the American Diabetes Association standards (ADA, 2017) and on stable dose of metformin for at least 6 weeks prior to screening and HbA1c at screening visit of ≥42 mmol/mol (6.0%) and ≤75 mmol/mol (9.0%) measured at local hospital laboratory.
- No significant signs or symptoms of coronary artery disease or, if known coronary artery disease, currently free of symptoms and a) all major epicardial vessels with <50% stenosis within 12 months prior to screening, or b) if revascularized with all major epicardial vessels with <50% remaining stenosis after stenting or bypass surgery procedure determined between 3 and 12 months prior to screening.
Key exclusion criteria (26 listed)
- Blood pressure at screening that would require a change in blood pressure treatment over the study period or any of the following: systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg.
- History of stroke or other clinically significant cerebrovascular disease.
- Any of the following cardiovascular diseases known within 3 months prior to signing the consent at enrolment:
- Planned cardiac surgery or angioplasty within 3 months from enrolment.
- Clinical diagnosis of type 1 diabetes, maturity onset diabetes of the young (MODY), secondary diabetes or diabetes insipidus.
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 |
|---|---|---|
| dapagliflozinAlso: Forxiga 10mgdapagliflozin 10mg | Drug | dapagliflozin 10mg |
| placeboplacebo to match dapagliflozin | Drug | placebo |
Primary outcome
Adjusted Mean Change From Baseline in Global Longitudinal Strain of the Left Ventricle (GLSLV) at End of Treatment.
Time frame: Baseline (Day 1) and end of treatment (Day 42)
Patients underwent magnetic resonance imaging (MRI) examination to determine the GLSLV, which is expressed as a percentage. The least square mean (LSM) change from baseline estimates were generated from an analysis of covariance (ANCOVA) model with treatment and baseline value of the endpoint as covariates.
1 secondary outcome
Adjusted Mean Change From Baseline in Myocardial Efficiency at End of Treatment.
Time frame: Baseline (Day 1) and end of treatment (Day 42)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- redacted SAPLink provided by the sponsor.
- redacted CSPLink provided by the sponsor.
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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.
Jonas Oldgren, MD, PhD principal investigator
Uppsala Clinical Research Center, Upppsala Sweden
Pirjo Nuutila, MD, PhD principal investigator
University of Turku, Turku, Finland
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing dapagliflozin in people with Diabetes Mellitus Type 2, run by AstraZeneca at 2 sites in 2 countries.
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 7 inclusion and 26 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: finished, as of the sponsor's last update on 27 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Finland, Sweden. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Adjusted Mean Change From Baseline in Global Longitudinal Strain of the Left Ventricle (GLSLV) at End of Treatment. (time frame: Baseline (Day 1) and end of treatment (Day 42)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Apr 2020.