Dapagliflozin for Acute Heart Failure

Overseen By Abby Cange

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The TIMI Study Group

Must not be taking: SGLT2 inhibitors

Disqualifiers: Type 1 diabetes, Recent MI, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether dapagliflozin, an SGLT2 inhibitor, can aid patients hospitalized for acute heart failure. The researchers aim to determine if starting this treatment in the hospital reduces the risk of heart-related death or improves heart failure symptoms. Participants will receive either dapagliflozin or a placebo, a pill with no active medicine, for two months. Ideal candidates are patients currently hospitalized with worsening heart failure symptoms, such as shortness of breath or swelling, who have had their treatments adjusted during their hospital stay. As a Phase 4 trial, this research seeks to understand how this FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using an SGLT2 inhibitor. It's best to discuss your specific medications with the trial team.

What is the safety track record for dapagliflozin?

Research has shown that dapagliflozin is safe for patients with sudden heart failure. Studies have found that starting dapagliflozin early during a hospital stay does not significantly increase risks. Important safety concerns include low blood pressure and changes in kidney function, though these were uncommon. The FDA has approved dapagliflozin for other heart conditions, supporting its safety for heart failure patients. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Dapagliflozin is unique because it offers a different approach to treating acute heart failure by targeting the kidneys to remove excess sodium and water from the body. Most treatments for heart failure focus on improving heart function directly, but dapagliflozin uses a mechanism called SGLT2 inhibition, which primarily affects glucose and fluid regulation. This can lead to rapid symptom relief and potentially better heart outcomes, which is why researchers are excited about its potential benefits over traditional options like beta-blockers and ACE inhibitors.

What is the effectiveness track record for dapagliflozin in treating acute heart failure?

Research has shown that dapagliflozin, which participants in this trial may receive, effectively treats heart failure. It reduces the risk of hospitalization for heart failure by 24%. For patients already hospitalized due to heart failure, it lowers the risk of dying from heart-related issues or worsening heart failure by 29%. Dapagliflozin also decreases the chances of dying from heart problems while in the hospital and reduces the likelihood of needing to return to the hospital within 30 days for those with sudden heart failure. Additionally, it improves the body's ability to eliminate excess fluid. Overall, dapagliflozin offers proven benefits in managing heart failure. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults hospitalized with acute heart failure who are stable after treatment. They should have a history of heart failure, no untreated serious arrhythmias or heart blocks, and not be at risk of pregnancy. People with type 1 diabetes, severe kidney issues, recent major heart procedures or those on certain other treatments can't join.

Inclusion Criteria

I am in the hospital for acute heart failure and meet specific treatment criteria.

Your heart's pumping ability has been measured within the past year.

People with and without type 2 diabetes can take part in the study.

Exclusion Criteria

I have type 1 diabetes or have had diabetic ketoacidosis.

I have experienced symptoms of low blood pressure in the last day.

Any condition that, in the opinion of the investigator, would compromise compliance with the trial protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dapagliflozin or placebo orally once daily for 2 months

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dapagliflozin
• Placebo

Trial Overview The study tests if starting dapagliflozin in the hospital helps prevent cardiovascular death or worsening heart failure compared to a placebo. It's an international study where patients are randomly assigned to either the drug or placebo group while still hospitalized.

How Is the Trial Designed?

Group I: Dapagliflozin Experimental Treatment 1 Intervention

Dapagliflozin 10 mg administered orally once daily for 2 months

Group II: Placebo Placebo Group 1 Intervention

Matching placebo administered orally once daily for 2 months

Dapagliflozin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Forxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in United States as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Approved in Canada as Farxiga for:

• Type 2 diabetes
• Heart failure
• Chronic kidney disease

Who Is Running the Clinical Trial?

The TIMI Study Group

Lead Sponsor

Trials

22

Recruited

129,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Published Research Related to This Trial

Dapagliflozin is an effective SGLT2 inhibitor for managing type 2 diabetes, showing consistent reductions in blood glucose levels and body weight over long-term follow-up periods of 1-4 years across various clinical trials.

It has a low risk of causing hypoglycemia and is generally well tolerated, although it can lead to genital infections, particularly in women, and is not recommended for patients with moderate to severe renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: a review of its use in patients with type 2 diabetes. Plosker, GL.[2022]

Dapagliflozin, an SGLT2 inhibitor, has been shown to significantly reduce the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF), regardless of whether they have type 2 diabetes.

In the DAPA-HF trial, dapagliflozin was well tolerated and demonstrated a lower risk of worsening heart failure or cardiovascular death compared to placebo, making it a valuable treatment option for adults with symptomatic HFrEF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction. Blair, HA.[2022]

Dapagliflozin (Farxiga) is approved for reducing the risk of declining kidney function and kidney failure in adults with chronic kidney disease, regardless of whether they have type 2 diabetes.

It also helps lower the risk of cardiovascular death and hospitalization for heart failure, highlighting its efficacy in managing both kidney and heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic Drug Approved to Reduce Risk of Kidney Disease. Aschenbrenner, DS.[2023]

Dapagliflozin (DAPA) is an effective SGLT2 inhibitor for treating type 2 diabetes, showing favorable pharmacokinetics and pharmacodynamics that help lower blood sugar levels while having beneficial effects on other metabolic risk factors.

While DAPA is generally safe, it carries an increased risk of genital and urinary infections, and concerns about bladder cancer and cardiovascular safety remain, prompting the FDA to seek further data on these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. Maranghi, M., Carnovale, A., Durante, C., et al.[2021]

The DICTATE-AHF trial is investigating the safety and efficacy of starting dapagliflozin within the first 24 hours of hospitalization for acute heart failure (AHF) in patients with type 2 diabetes, with a planned enrollment of 240 patients.

The primary goal is to assess how well dapagliflozin improves diuretic response compared to usual care, while also monitoring for safety issues like hypoglycemia and kidney function, which are crucial for managing both heart failure and diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dapagliflozin in acute heart failure: Rationale and design of the DICTATE-AHF trial. Cox, ZL., Collins, SP., Aaron, M., et al.[2021]

Dapagliflozin is an effective treatment for type 2 diabetes, proven through multiple controlled clinical trials that assess its efficacy, safety, and tolerability.

It is approved by the FDA for use as a standalone therapy or in combination with other glucose-lowering medications, including insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. Davis, PN., Ndefo, UA., Oliver, A.[2021]

A randomized controlled trial (RCT) showed that dapagliflozin significantly improves cardiovascular outcomes in heart failure patients, regardless of whether they have diabetes.

This suggests that dapagliflozin may be an effective treatment option for enhancing heart health in a broad range of heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribe an SGLT2 inhibitor for heart failure in the absence of diabetes? Koenigsberger, D., Marquez, A., Hughes, PR.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10453961/

Effect of Dapagliflozin in Patients with Heart Failure Additionally, dapagliflozin significantly reduced the hospitalization due to heart failure (RR = 0.76, 95% CI: 0.70–0.84, P > 0.00001, I2 = 0%) ...

2. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.076575

Dapagliflozin in Patients Hospitalized for Heart Failure In a meta-analysis of patients hospitalized for HF, SGLT2i reduced the early risk of cardiovascular death or worsening HF (HR, 0.71; 95% CI, ...

3. bmccardiovascdisord.biomedcentral.com bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-024-04412-x

Dapagliflozin in acute heart failure management: a systematic ... Dapagliflozin appears to be beneficial in reducing In-Hospital Cardiovascular mortality and 30-day hospital readmissions in AHF patients.

4. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2022/new-data-show-farxiga-significantly-lowers-the-risk-of-cardiovascular-death-in-patients-with-heart-failure.html

New data show FARXIGA significantly lowers the risk of ... Pre-specified pooled analysis from Phase III trials demonstrated reduction in CV death by 14% and reduction in death from any cause by 10% in patients with ...

5. jacc.org jacc.org/doi/10.1016/j.jacc.2024.02.009

Efficacy and Safety of Dapagliflozin in Patients With Acute ... Dapagliflozin improved multiple measures of diuretic efficacy. The primary outcome of weight-based diuretic efficiency favored dapagliflozin ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39731023/

Dapagliflozin in acute heart failure management Dapagliflozin significantly reduced In-Hospital Cardiovascular mortality (RR 0.56, 95% CI 0.36-0.88, p = 0.01, I²=26%) and 30-day hospital ...

7. farxiga-hcp.com farxiga-hcp.com/heart-failure

Heart Failure | FARXIGA® (dapagliflozin) 5 mg & 10 mg tablets FARXIGA HELPS PATIENTS LIVE LONGER AND STAY OUT OF THE HOSPITAL · FARXIGA Significantly Reduced the Risk of CV Death or Hospitalization for HF Across the Range ...