Dapagliflozin for Acute Heart Failure

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: The TIMI Study Group

Must not be taking: SGLT2 inhibitors

Disqualifiers: Type 1 diabetes, Recent MI, others

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is an international, multicenter, parallel-group, randomized, double-blind, placebo-controlled trial in patients who have been stabilized during hospitalization for acute heart failure, evaluating the effect of in-hospital initiation of dapagliflozin versus placebo on the clinical outcome of cardiovascular death or worsening heart failure.

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 data supports the effectiveness of the drug Dapagliflozin for acute heart failure?

Research shows that Dapagliflozin, a drug used for heart failure with reduced ejection fraction, significantly lowers the risk of heart-related death or hospitalization for heart failure, even in patients without diabetes. This suggests it could be effective for acute heart failure as well. ^{1 2 3 4 5}

Is dapagliflozin generally safe for humans?

Dapagliflozin, also known as Farxiga or Forxiga, is generally well tolerated in humans. It has been used safely in treating heart failure and type 2 diabetes, with common side effects including genital infections, especially in women. It is not recommended for people with moderate or severe kidney problems. ^{1 2 4 5 6}

What makes the drug dapagliflozin unique for treating acute heart failure?

Dapagliflozin is unique because it is a sodium-glucose cotransporter-2 (SGLT2) inhibitor that not only helps manage blood sugar levels in diabetes but also reduces the risk of cardiovascular death and worsening heart failure. It can be started early during an acute heart failure hospitalization to help with fluid removal and improve heart function, making it a novel option for both heart failure and diabetes management. ^{1 2 5 6 7}

Research Team

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Dapagliflozin (SGLT2 Inhibitor)
• Placebo (Drug)

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.

Participant Groups

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 Canada for the following indications:

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+

Peter Benton

Worldwide Clinical Trials

Chief Executive Officer since 2024

MBA in Finance and Strategy from The Wharton School, University of Pennsylvania; Bachelor's degree in Mechanical Engineering from Northeastern University

Dr. Michael F. Murphy

Worldwide Clinical Trials

Chief Medical Officer since 1997

MD and PhD in Pharmacology with training at Tulane University, Stanford University, and Mt. Sinai School of Medicine

Findings from Research

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 (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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics and clinical efficacy of dapagliflozin for the treatment of type 2 diabetes. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Prescribe an SGLT2 inhibitor for heart failure in the absence of diabetes? [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Dapagliflozin: A Sodium Glucose Cotransporter 2 Inhibitor for the Treatment of Diabetes Mellitus. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. New Zealand pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dapagliflozin in acute heart failure: Rationale and design of the DICTATE-AHF trial. [2021]