Cardiovascular DiseasesPhase 2/3DECODEDNCT04764097
Dapagliflozin Effect on Cardiovascular Outcomes in Haemodialysis for End Stage Renal Disease
A Phase 2/3 study testing Dapagliflozin in people with Cardiovascular Diseases and End Stage Renal Disease, run by Tan Tock Seng Hospital.
Trial summary
This study aims to study SGLT2 inhibitors in patients who are undergoing haemodialysis for end stage renal disease and established ASCVD, to examine the safety and clinical outcomes, consisting of a composite of non-fatal stroke, non-fatal myocardial infarction, or cardiovascular death as the primary outcome. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Cardiovascular Diseases, End Stage Renal Disease
- 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
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2021to Jun 2026
- Phase
- Phase 2/3
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent prior to any study specific procedures.
- Female or male aged ≥ 21 years.
- Undergoing haemodialysis for end stage renal disease regardless of cause and previous cardiac events.
Who cannot join
- Diagnosis of Type 1 diabetes mellitus.
- Pregnant or planning pregnancy or breast-feeding patients.
- Any clinical condition that would jeopardize patient safety while participating in this clinical trial.
- Intake of an investigational drug or participating in another clinical trial involving an investigational drug.
- Life limiting disease other than ESRD with life expectancy estimated to be less than 12 month.
About this study
Official title: A Multi-centre, Randomised, Double-blind, Placebo-controlled Trial to Determine the Effect of Dapagliflozin 10mg Once Daily on Cardiovascular Outcomes in Haemodialysis for Patients With End Stage Renal Disease (ESRD)
This study aims to study SGLT2 inhibitors in patients who are undergoing haemodialysis for end stage renal disease and established ASCVD, to examine the safety and clinical outcomes, consisting of a composite of non-fatal stroke, non-fatal myocardial infarction, or cardiovascular death as the primary outcome. The key secondary composite outcome was all cause death or hospitalization for unstable angina.
Read the detailed description
Cardiovascular disease accounts for more than 50% of end-stage renal disease (ESRD) deaths. The reported cardiovascular death rates in patients receiving dialysis are substantially higher than in the general population. Cardiovascular mortality in ESRD is particularly high after acute myocardial infarction, but it is also elevated in ESRD patients with other forms of atherosclerotic vascular disease (eg, chronic coronary artery disease, strokes, transient ischemic attacks, and peripheral arterial disease). Left ventricular hypertrophy and dilation are associated with increased cardiovascular mortality, as is congestive heart failure. One of the major reasons for such high cardiovascular mortality in ESRD is the large burden of cardiovascular disease present in patients with chronic artery disease before renal replacement therapy.
SGLT2 inhibitors have demonstrated benefits in reduction of major adverse cardiac events and heart failure hospitalisation in phase 3 randomised controlled trials. In addition, several recent clinical publications have also indicated renal benefits in patients with chronic renal impairment (eGFR >30ml/min).
The primary SGLT2 inhibition predominantly occurs at the proximal tubules of kidneys. The mechanistic benefits postulated (other than serum glucose lowering) included SGL2i mediated naturesis and glucosuria. Independent of this class's effects at the renal level, SGL2i possibly affect cardiac metabolism (in animal studies), with reverse adverse cardiac remodelling by switching myocardial substrate utilization from glucose toward oxidation of fatty acids, ketone bodies and branch-chained amino acids. Such improvement in cardiac metabolism may attenuate myocardial ischemia, improve cardiac haemodynamics and reduce overall cardiac mortality, either independent of or synergistic with SGLT2 inhibition at the kidney level.
Currently, there is a gap in knowledge and paucity of safety, efficacy and clinical outcomes data for the use of SGLT2 inhibitors in patients who are undergoing haemodialysis for end stage renal disease and established ASCVD.
This study aims to study SGLT2 inhibitors in this population and examine the safety and clinical outcomes, consisting of a composite of non-fatal stroke, non-fatal myocardial infarction, or cardiovascular death as the primary outcome. The key secondary composite outcome was all cause death or hospitalization for unstable angina.
- Conditions
- Cardiovascular Diseases, End Stage Renal Disease
- Being tested
- Dapagliflozin, Placebo
- Keywords
- Cardiovascular Outcomes, Renal Disease, Dapagliflozin, SGLT2 Inhibitor
- Medical subject headings
- Cardiovascular Diseases, Kidney Failure, Chronic, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DapagliflozinDrug
SGTL2 Inhibitor
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin | Experimental | Dapagliflozin, Oral Tablet,10mg, od, 24 months. Receives: Drug: Dapagliflozin |
| Placebo | Placebo comparator | Placebo, Oral Tablet, od, 24 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subjects included in the composite endpoint of cardiovascular death, myocardial infarction or ischemic stroke (time to first or recurrent event).
Data will be derived from 3 monthly telephone follow-up and 6monthly physical site visits and events are documented in eCRF
Measured: Up to 3 years
Secondary outcomes (1)
Subjects included in the composite endpoint of all-cause death or hospitalization for unstable angina (time to first or recurrent event).
Data will be derived from 3 monthly telephone follow-up and 6monthly physical site visits and events are documented in eCRF
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study startJun 2021 (estimated)
- Primary completionJun 2025 (estimated)
- Study completionJun 2026 (estimated)
Why it stopped: Lack of funding and similar competing study being conducted in Europe.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseasesStudies 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 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised (1:1) to either Dapaglifozin 10mg or placebo.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tan Tock Seng Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Foo Chee Guan, Tan Tock Seng Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04764097
- Sponsor's protocol ID
- TTSH-DECODED
- Acronym
- DECODED
- Status last verified
- Oct 2021
- First submitted
- 18 Feb 2021
- Last updated
- 21 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-centre, Randomised, Double-blind, Placebo-controlled Trial to Determine the Effect of Dapagliflozin 10mg Once Daily on Cardiovascular Outcomes in Haemodialysis for Patients With End Stage Renal Disease (ESRD)
- ClinicalTrials.gov ID
- NCT04764097
- Acronym / sponsor ID
- DECODED / TTSH-DECODED
- Conditions
- Cardiovascular Diseases, End Stage Renal Disease
- Keywords
- Cardiovascular Outcomes, Renal Disease, Dapagliflozin, SGLT2 Inhibitor
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding and similar competing study being conducted in Europe.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Tan Tock Seng HospitalUniversity, hospital or other
- Study start
- Jun 2021 (estimated)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 21 Feb 2021 (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.
This study aims to study SGLT2 inhibitors in patients who are undergoing haemodialysis for end stage renal disease and established ASCVD, to examine the safety and clinical outcomes, consisting of a composite of non-fatal stroke, non-fatal myocardial infarction, or cardiovascular death as the primary outcome. The key secondary composite outcome was all cause death or hospitalization for unstable angina.
Detailed description
Cardiovascular disease accounts for more than 50% of end-stage renal disease (ESRD) deaths. The reported cardiovascular death rates in patients receiving dialysis are substantially higher than in the general population. Cardiovascular mortality in ESRD is particularly high after acute myocardial infarction, but it is also elevated in ESRD patients with other forms of atherosclerotic vascular disease (eg, chronic coronary artery disease, strokes, transient ischemic attacks, and peripheral arterial disease). Left ventricular hypertrophy and dilation are associated with increased cardiovascular mortality, as is congestive heart failure. One of the major reasons for such high cardiovascular mortality in ESRD is the large burden of cardiovascular disease present in patients with chronic artery disease before renal replacement therapy.
SGLT2 inhibitors have demonstrated benefits in reduction of major adverse cardiac events and heart failure hospitalisation in phase 3 randomised controlled trials. In addition, several recent clinical publications have also indicated renal benefits in patients with chronic renal impairment (eGFR >30ml/min).
The primary SGLT2 inhibition predominantly occurs at the proximal tubules of kidneys. The mechanistic benefits postulated (other than serum glucose lowering) included SGL2i mediated naturesis and glucosuria. Independent of this class's effects at the renal level, SGL2i possibly affect cardiac metabolism (in animal studies), with reverse adverse cardiac remodelling by switching myocardial substrate utilization from glucose toward oxidation of fatty acids, ketone bodies and branch-chained amino acids. Such improvement in cardiac metabolism may attenuate myocardial ischemia, improve cardiac haemodynamics and reduce overall cardiac mortality, either independent of or synergistic with SGLT2 inhibition at the kidney level.
Currently, there is a gap in knowledge and paucity of safety, efficacy and clinical outcomes data for the use of SGLT2 inhibitors in patients who are undergoing haemodialysis for end stage renal disease and established ASCVD.
This study aims to study SGLT2 inhibitors in this population and examine the safety and clinical outcomes, consisting of a composite of non-fatal stroke, non-fatal myocardial infarction, or cardiovascular death as the primary outcome. The key secondary composite outcome was all cause death or hospitalization for unstable angina.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Randomised (1:1) to either Dapaglifozin 10mg or placebo.
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin | Experimental | Drug: DapagliflozinDapagliflozin, Oral Tablet,10mg, od, 24 months. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo, Oral Tablet, od, 24 months. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Provision of informed consent prior to any study specific procedures.
- Female or male aged ≥ 21 years.
- Undergoing haemodialysis for end stage renal disease regardless of cause and previous cardiac events.
Key exclusion criteria (5 listed)
- Diagnosis of Type 1 diabetes mellitus.
- Pregnant or planning pregnancy or breast-feeding patients.
- Any clinical condition that would jeopardize patient safety while participating in this clinical trial.
- Intake of an investigational drug or participating in another clinical trial involving an investigational drug.
- Life limiting disease other than ESRD with life expectancy estimated to be less than 12 month.
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 |
|---|---|---|
| DapagliflozinSGTL2 Inhibitor | Drug | Dapagliflozin |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Subjects included in the composite endpoint of cardiovascular death, myocardial infarction or ischemic stroke (time to first or recurrent event).
Time frame: Up to 3 years
Data will be derived from 3 monthly telephone follow-up and 6monthly physical site visits and events are documented in eCRF
1 secondary outcome
Subjects included in the composite endpoint of all-cause death or hospitalization for unstable angina (time to first or recurrent event).
Time frame: Up to 3 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 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.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dapagliflozin in people with Cardiovascular Diseases and End Stage Renal Disease, run by Tan Tock Seng Hospital.
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 3 inclusion and 5 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: withdrawn, as of the sponsor's last update on 21 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 withdrawn before enrolling participants, so there are no results.
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?
Subjects included in the composite endpoint of cardiovascular death, myocardial infarction or ischemic stroke (time to first or recurrent event). (time frame: Up to 3 years). 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 21 Oct 2021.