Heart FailurePhase 4RECEDE-CHFNCT03226457
SGLT2 Inhibition in Combination With Diuretics in Heart Failure
A Phase 4 study testing Empagliflozin 25mg and Frusemide in people with Heart Failure and Type 2 Diabetes Mellitus, run by University of Dundee at 1 site in United Kingdom.
Trial summary
The RECEDE-CHF trial is a single centre phase IV, randomised, double-blind, placebo-controlled, crossover trial conducted in NHS Tayside, Scotland comparing empagliflozin 25mg, to placebo in patients with Type 2 Diabetes and mild Chronic Heart Failure with left ventricular systolic dysfunction who are already on a… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure, Type 2 Diabetes Mellitus
- What is being tested?
- Empagliflozin 25mg and Frusemide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 Dec 2017to 9 Jan 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of NYHA Functional class II-III HF with prior echocardiographic evidence of LVSD.
- On stable doses of furosemide, or alternative loop diuretic for at least one month.
- Stable Type 2 Diabetes (HbA1c, in the last 3 months, of 6.5% ≤ and ≤10.0%)
- eGFR ≥ 45 ml/min.
- Have stable HF symptoms for at least three months prior to consent
- On stable HF therapy for at least three months prior to consent
- Have not been hospitalised for HF for at least three months prior to consent.
- Women of childbearing potential must agree to take precautions to avoid pregnancy throughout the trial and for 4 weeks after intake of the last dose.
Who cannot join
- A diagnosis of chronic liver disease and/or liver enzymes that are twice the upper limit of normal
- Systolic BP of <95mmHg at screening visit.
- Participants on thiazide diuretics.
- Participants receiving renal dialysis
- Participants who have previously had an episode of diabetic ketoacidosis.
- Participants with type 1 diabetes mellitus
Show all 14Show fewer
- Malignancy (receiving active treatment) or other life threatening disease.
- Pregnant or lactating women
- Participants with difficulty in micturition e.g. severe prostate enlargement
- Allergy to any SGLT2 inhibitor or lactose or galactose intolerance
- Past or current treatment with any SGLT2 inhibitor
- Participants who have participated in any other clinical interventional trial of an investigational medicinal product within 30 days.
- Participants who are unable to give informed consent
- Any other reason considered by the physician to be inappropriate for inclusion.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Dundee, Ninewells Hospital and Medical School
Dundee, Angus, DD1 9SY
About this study
Official title: Renal and Cardiovascular Effect of Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibition in Combination With Loop Diuretics in Diabetic Patients With Chronic Heart Failure
The RECEDE-CHF trial is a single centre phase IV, randomised, double-blind, placebo-controlled, crossover trial conducted in NHS Tayside, Scotland comparing empagliflozin 25mg, to placebo in patients with Type 2 Diabetes and mild Chronic Heart Failure with left ventricular systolic dysfunction who are already on a loop diuretic. Renal physiological testing will be performed at two points on each arm to assess the effect of empagliflozin, on urinary volume, compared to placebo. The secondary outcomes are to assess the effect of empagliflozin in addition to loop diuretics on natriuresis, to assess the safety of add-on SGLT2 inhibitor therapy as measured by changes to serum creatinine and eGFR, to assess effects of empagliflozin on urinary protein/creatinine ratio, albumin/creatinine ratio and cystatin C when compared to placebo.
Read the detailed description
Type 2 Diabetes (T2D) and Heart Failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium-glucose co-transporter 2 (SGLT2) inhibitors and their use in patients with HF. This is following publication of EMPA-REG OUTCOME trial that reported a 14% reduction in the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and >30% reductions in cardiovascular mortality, overall mortality and HF hospitalisations in patients randomised to the SGLT2 inhibitor, empagliflozin, when compared to placebo. Data on the effect of SGLT2 inhibitor use with diuretics is limited. We hypothesize that, in the diabetic CHF population, SGLT2 inhibition may augment the effects of loop diuretics.
Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. The investigational medicinal product will be administered, followed by an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose.
This proof of concept trial will aim to shed light on the mechanism of the cardiovascular and renal outcomes demonstrated in the recent EMPA-REG study by documenting the influence of the SGLT2 inhibitors when used in combination with a loop diuretic on diuresis and natriuresis when compared to placebo.
The RECEDE-CHF trial is funded by the British Heart Foundation (BHF grant number: 807998). NAM is a BHF funded clinical research fellow.
- Conditions
- Heart Failure, Type 2 Diabetes Mellitus
- Being tested
- Empagliflozin 25mg, Placebo oral capsule, Frusemide
- Keywords
- Heart Failure, Type 2 Diabetes Mellitus, Sodium-Glucose co-Transporter 2 (SGLT2) inhibitors, Natriuresis, Diuresis
- Medical subject headings
- Heart Failure, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Empagliflozin 25mgDrug
Also called Jardiance
Empagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks
Placebo oral capsuleDrug
Also called Placebo
Capsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks
FrusemideDrug
Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin/Placebo | Active comparator | Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks, minimum of a 2 week washout period, then 6 weeks placebo Receives: Drug: Empagliflozin 25mg; Drug: Placebo oral capsule; Drug: Frusemide |
| Placebo/Empagliflozin | Active comparator | Placebo for 6 weeks, minimum of a 2 week washout period, followed by Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks Receives: Drug: Empagliflozin 25mg; Drug: Placebo oral capsule; Drug: Frusemide |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Effect of Empagliflozin Versus Placebo on the Change in Urine Output.
Change from urinary volume from baseline (mls).
Measured: Change from baseline to 6 weeks
Secondary outcomes (6)
The Effect of Empagliflozin Versus Placebo on the Change in Urinary Sodium Excretion.
The effect of empagliflozin versus placebo on the change in urinary sodium excretion: change in fractional urinary sodium excretion from baseline (%).
Measured: Change from baseline to 6 weeks
Number of Participants With a Change in CKD Category as Dictated by the Glomerular Filtration Rate
The effect of empagliflozin versus placebo on the change in glomerular filtration rate: Change in estimated glomerular filtration rate from baseline (ml/min/1.73m2).
Data was recorded as a persistent reduction in CKD category in the empagliflozin group versus placebo
Measured: From baseline to 6 weeks
The Effect of Empagliflozin Versus Placebo on the Change in Serum Creatinine.
Change in serum creatinine from baseline (mmol/L).
Measured: Change from baseline to 6 weeks
The Effect of Empagliflozin Versus Placebo on the Change to Urinary Protein/Creatinine Ratio.
The effect of empagliflozin versus placebo on the change to urinary protein/creatinine ratio: Change in urinary protein/creatinine ratio from baseline (mg/mmol).
Measured: Change from baseline to 6 weeks
The Effect of Empagliflozin Versus Placebo on the Change to Urinary Albumin/Creatinine Ratio.
The effect of empagliflozin versus placebo on the change to urinary albumin/creatinine ratio: Change in urinary albumin/creatinine ratio from baseline (mg/mmol).
Measured: Change from baseline to 6 weeks
The Effect of Empagliflozin Versus Placebo on the Change to the Renal Biomarker, Cystatin C.
The effect of empagliflozin versus placebo on the change to the renal biomarker, cystatin C: Change in Cystatin C from baseline (ng/ml).
Measured: Change from baseline to 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start11 Dec 2017
- Primary completion11 Dec 2018
- Study completion9 Jan 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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 6 week period of Investigational Medicinal Product (Empagliflozin 25 mg od) or placebo. A 2 week washout period will then be observed, followed by the second arm with a further 6 week period of placebo or IMP. At week 1 and week 6 of each arm, detailed Renal Physiology Test days will be performed.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation
- Responsible party
- Principal investigator, Natalie Mordi, University of Dundee
- Investigators
- Natalie A Mordi, MBChB MRCP, Principal investigator, University of Dundee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03226457
- Sponsor's protocol ID
- BHF:807998
- Acronym
- RECEDE-CHF
- Status last verified
- Jun 2021
- First submitted
- 17 Jul 2017
- Last updated
- 30 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Mordi NA, Mordi IR, Singh JS, McCrimmon RJ, Struthers AD, Lang CC. Renal and Cardiovascular Effects of SGLT2 Inhibition in Combination With Loop Diuretics in Patients With Type 2 Diabetes and Chronic Heart Failure: The RECEDE-CHF Trial. Circulation. 2020 Nov 3;142(18):1713-1724. doi: 10.1161/CIRCULATIONAHA.120.048739. Epub 2020 Aug 29.
PubMed 32865004Mordi NA, Mordi IR, Singh JS, Baig F, Choy AM, McCrimmon RJ, Struthers AD, Lang CC. Renal and Cardiovascular Effects of sodium-glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial. BMJ Open. 2017 Oct 16;7(10):e018097. doi: 10.1136/bmjopen-2017-018097.
PubMed 29042392
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renal and Cardiovascular Effect of Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibition in Combination With Loop Diuretics in Diabetic Patients With Chronic Heart Failure
- ClinicalTrials.gov ID
- NCT03226457
- Acronym / sponsor ID
- RECEDE-CHF / BHF:807998
- Conditions
- Heart Failure, Type 2 Diabetes Mellitus
- Keywords
- Heart Failure, Type 2 Diabetes Mellitus, Sodium-Glucose co-Transporter 2 (SGLT2) inhibitors, Natriuresis, Diuresis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Collaborators
- British Heart Foundation
- Study start
- 11 Dec 2017 (actual)
- Primary completion
- 11 Dec 2018 (actual)
- Study completion
- 9 Jan 2019 (actual)
- First posted
- 21 Jul 2017 (actual)
- Results
- Posted 30 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The RECEDE-CHF trial is a single centre phase IV, randomised, double-blind, placebo-controlled, crossover trial conducted in NHS Tayside, Scotland comparing empagliflozin 25mg, to placebo in patients with Type 2 Diabetes and mild Chronic Heart Failure with left ventricular systolic dysfunction who are already on a loop diuretic. Renal physiological testing will be performed at two points on each arm to assess the effect of empagliflozin, on urinary volume, compared to placebo. The secondary outcomes are to assess the effect of empagliflozin in addition to loop diuretics on natriuresis, to assess the safety of add-on SGLT2 inhibitor therapy as measured by changes to serum creatinine and eGFR, to assess effects of empagliflozin on urinary protein/creatinine ratio, albumin/creatinine ratio and cystatin C when compared to placebo.
Detailed description
Type 2 Diabetes (T2D) and Heart Failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium-glucose co-transporter 2 (SGLT2) inhibitors and their use in patients with HF. This is following publication of EMPA-REG OUTCOME trial that reported a 14% reduction in the primary composite outcome of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and >30% reductions in cardiovascular mortality, overall mortality and HF hospitalisations in patients randomised to the SGLT2 inhibitor, empagliflozin, when compared to placebo. Data on the effect of SGLT2 inhibitor use with diuretics is limited. We hypothesize that, in the diabetic CHF population, SGLT2 inhibition may augment the effects of loop diuretics.
Renal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. The investigational medicinal product will be administered, followed by an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose.
This proof of concept trial will aim to shed light on the mechanism of the cardiovascular and renal outcomes demonstrated in the recent EMPA-REG study by documenting the influence of the SGLT2 inhibitors when used in combination with a loop diuretic on diuresis and natriuresis when compared to placebo.
The RECEDE-CHF trial is funded by the British Heart Foundation (BHF grant number: 807998). NAM is a BHF funded clinical research fellow.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 6 week period of Investigational Medicinal Product (Empagliflozin 25 mg od) or placebo. A 2 week washout period will then be observed, followed by the second arm with a further 6 week period of placebo or IMP. At week 1 and week 6 of each arm, detailed Renal Physiology Test days will be performed.
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin/Placebo | Active comparator | Drug: Empagliflozin 25mg, Drug: Placebo oral capsule, Drug: FrusemideEmpagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks, minimum of a 2 week washout period, then 6 weeks placebo |
| Placebo/Empagliflozin | Active comparator | Drug: Empagliflozin 25mg, Drug: Placebo oral capsule, Drug: FrusemidePlacebo for 6 weeks, minimum of a 2 week washout period, followed by Empagliflozin (SGLT2 inhibitor) 25mg capsules once daily for 6 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of NYHA Functional class II-III HF with prior echocardiographic evidence of LVSD.
- On stable doses of furosemide, or alternative loop diuretic for at least one month.
- Stable Type 2 Diabetes (HbA1c, in the last 3 months, of 6.5% ≤ and ≤10.0%)
- eGFR ≥ 45 ml/min.
- Have stable HF symptoms for at least three months prior to consent
Key exclusion criteria (14 listed)
- A diagnosis of chronic liver disease and/or liver enzymes that are twice the upper limit of normal
- Systolic BP of <95mmHg at screening visit.
- Participants on thiazide diuretics.
- Participants receiving renal dialysis
- Participants who have previously had an episode of diabetic ketoacidosis.
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 |
|---|---|---|
| Empagliflozin 25mgAlso: JardianceEmpagliflozin (SGLT2 inhibitor) 25 mg once daily for 6 weeks | Drug | Empagliflozin/Placebo, Placebo/Empagliflozin |
| Placebo oral capsuleAlso: PlaceboCapsules containing microcrystalline cellulose Ph Eur over encapsulated in a hard gelatine capsule shell to match the active comparator once daily for 6 weeks | Drug | Empagliflozin/Placebo, Placebo/Empagliflozin |
| FrusemideRenal Physiology Test (RPT) days will be performed at week 1 and week 6 on each arm of this crossover trial. On these RPT days participants will undergo oral water loading (15mls/kg) and frequent urination at 30 minute intervals to gain a steady state diuresis. At a set time point, an intravenous bolus of furosemide at a dose of half the participant's usual loop diuretic dose will be administered. | Drug | Empagliflozin/Placebo, Placebo/Empagliflozin |
Primary outcome
The Effect of Empagliflozin Versus Placebo on the Change in Urine Output.
Time frame: Change from baseline to 6 weeks
Change from urinary volume from baseline (mls).
6 secondary outcomes
The Effect of Empagliflozin Versus Placebo on the Change in Urinary Sodium Excretion.
Time frame: Change from baseline to 6 weeks
Number of Participants With a Change in CKD Category as Dictated by the Glomerular Filtration Rate
Time frame: From baseline to 6 weeks
The Effect of Empagliflozin Versus Placebo on the Change in Serum Creatinine.
Time frame: Change from baseline to 6 weeks
The Effect of Empagliflozin Versus Placebo on the Change to Urinary Protein/Creatinine Ratio.
Time frame: Change from baseline to 6 weeks
The Effect of Empagliflozin Versus Placebo on the Change to Urinary Albumin/Creatinine Ratio.
Time frame: Change from baseline to 6 weeks
The Effect of Empagliflozin Versus Placebo on the Change to the Renal Biomarker, Cystatin C.
Time frame: Change from baseline to 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32865004Mordi NA, Mordi IR, Singh JS, McCrimmon RJ, Struthers AD, Lang CC. Renal and Cardiovascular Effects of SGLT2 Inhibition in Combination With Loop Diuretics in Patients With Type 2 Diabetes and Chronic Heart Failure: The RECEDE-CHF Trial. Circulation. 2020 Nov 3;142(18):1713-1724. doi: 10.1161/CIRCULATIONAHA.120.048739. Epub 2020 Aug 29.
- Derived from this study: PubMed 29042392Mordi NA, Mordi IR, Singh JS, Baig F, Choy AM, McCrimmon RJ, Struthers AD, Lang CC. Renal and Cardiovascular Effects of sodium-glucose cotransporter 2 (SGLT2) inhibition in combination with loop Diuretics in diabetic patients with Chronic Heart Failure (RECEDE-CHF): protocol for a randomised controlled double-blind cross-over trial. BMJ Open. 2017 Oct 16;7(10):e018097. doi: 10.1136/bmjopen-2017-018097.
- Individual participant dataSharing planned: Undecided
Related trials for Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
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.
Natalie A Mordi, MBChB MRCP principal investigator
University of Dundee
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Empagliflozin 25mg and Frusemide in people with Heart Failure and Type 2 Diabetes Mellitus, run by University of Dundee at 1 site in United Kingdom.
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 8 inclusion and 14 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 30 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 1 site in United Kingdom. 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 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 30 Jun 2021). 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?
The Effect of Empagliflozin Versus Placebo on the Change in Urine Output. (time frame: Change from baseline to 6 weeks). 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 NCT03226457, which also lists 2 linked publications.
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 30 Jun 2021.