Canagliflozin for Heart Disease

(CANTORSING Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Kevin Boczar, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Ottawa Heart Institute Research Corporation

Must not be taking: Antibiotics, Prednisone, Methotrexate, others

Disqualifiers: Severe LV dysfunction, Decompensated heart failure, Active infection, Active inflammatory conditions, Pregnancy, Breastfeeding, GFR <50, others

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

CANTOR SING is a pilot single center double blinded randomized study. The investigators will compare the effect of canagliflozin (300 mg daily - intervention arm) vs. placebo (control group) on the FDG aortic uptake in patients with stable CAD (over 60 days post-myocardial infarction) after a 6-month period of treatment. The investigators plan to enroll 8 patients in each arm (total sample size: 16 patients). Primary endpoint is the change in FDG aortic uptake between baseline and 6 months in each arm.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications, but you cannot participate if you are using certain medications like p-glycoprotein inhibitors or strong CYP3A4 inhibitors.

What evidence supports the effectiveness of the drug Canagliflozin for heart disease?

Research from the CANVAS Program shows that Canagliflozin, a drug used for type 2 diabetes, can lower the risk of heart-related problems like heart attacks and strokes in patients with high cardiovascular risk. This suggests it may be beneficial for heart disease. ^{1 2 3 4 5}

Is Canagliflozin safe for humans?

Canagliflozin, used for type 2 diabetes, has some serious side effects like severe ketoacidosis (a dangerous condition with high acid levels in the blood) and rare cases of acute pancreatitis (inflammation of the pancreas). It can also cause genital infections and, in some cases, low blood pressure, especially in older adults. ^{2 4 5 6 7}

How is the drug Canagliflozin unique for heart disease treatment?

Canagliflozin is unique because it works by blocking a protein in the kidneys that helps reabsorb sugar, which not only helps control blood sugar levels but also reduces hospitalizations for heart failure in people with type 2 diabetes. This dual benefit makes it different from many other heart disease treatments that do not address blood sugar control. ^{2 8 9 10 11}

Eligibility Criteria

This trial is for people who have stable coronary artery disease (CAD) at least 60 days after a heart attack and also have type 2 diabetes. Participants must be willing to give informed consent.

Inclusion Criteria

I have diabetes.

Given informed consent

I had a heart attack over 2 months ago and my heart condition has been stable since.

Exclusion Criteria

I am unable to understand and give consent for treatment.

My heart's pumping ability is significantly reduced.

Pregnancy (all women of childbearing potential will have a negative BHCG test)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either canagliflozin 300 mg or placebo daily for 6 months

6 months

3 visits (in-person) every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including clinical evaluation and blood collection

6 months

2 visits (in-person) at baseline and 6 months

Treatment Details

Interventions

• Canagliflozin (Sodium-glucose cotransporter 2 (SGLT2) inhibitor)
• Placebo (Drug)

Trial Overview The study compares Canagliflozin, a medication given daily, with a placebo over six months to see if it reduces inflammation in the blood vessels of patients with CAD and diabetes.

Participant Groups

Group I: Active Active Control 1 Intervention

Canagliflozin 300mg PO daily

Group II: Placebo Placebo Group 1 Intervention

Placebo PO daily

Canagliflozin is already approved in European Union, United States, Australia for the following indications:

🇪🇺 Approved in European Union as Invokana for:

• Type 2 diabetes mellitus
• Cardiovascular risk reduction

🇺🇸 Approved in United States as Invokana for:

• Type 2 diabetes mellitus
• Cardiovascular risk reduction
• Diabetic kidney disease

🇦🇺 Approved in Australia as Invokana for:

• Type 2 diabetes mellitus
• Cardiovascular risk reduction

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Ottawa Heart Institute Ottawa, Canada

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation Lead Sponsor

References

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

Canagliflozin: a review of its use in patients with type 2 diabetes mellitus. [2021] Canagliflozin (Invokana™) is an orally administered sodium-glucose co-transporter-2 (SGLT2) inhibitor used in the treatment of patients with type 2 diabetes. By inhibiting the transporter protein SGLT2 in the kidneys, canagliflozin reduces renal glucose reabsorption, thereby increasing urinary glucose excretion and reducing blood glucose levels. Several randomized placebo- or active comparator-controlled trials of 26-52 weeks' duration (plus extension phases) have shown that canagliflozin improves glycaemic control when used as monotherapy or as add-on therapy to metformin and/or other antihyperglycaemic agents, including insulin, in patients with type 2 diabetes. In addition to achieving reductions from baseline in glycosylated haemoglobin, canagliflozin also showed beneficial effects for other endpoints including reductions from baseline in fasting plasma glucose levels and bodyweight. Canagliflozin has a low risk of hypoglycaemia and was generally well tolerated in clinical trials. The most frequently reported adverse events with canagliflozin are female genital mycotic infections, urinary tract infections and increased urination. The pharmacodynamic response to canagliflozin declines with increasing severity of renal impairment, and prescribing information should be consulted regarding dosage adjustments or restrictions in moderate to severe renal dysfunction. Canagliflozin has modest effects on the serum lipid profile, some beneficial (increased high-density lipoprotein cholesterol and decreased triglycerides) and others not (increased low-density lipoprotein cholesterol). Most patients treated with canagliflozin also have a modest reduction in blood pressure. The overall effect of canagliflozin on the risk of cardiovascular disease is unknown and will be evaluated in the ongoing CANVAS trial; preliminary cardiovascular safety data suggest no increased risk. Thus, with its unique mechanism of action that is independent of insulin secretion and action, canagliflozin is a useful addition to the therapeutic options available for the management of type 2 diabetes, particularly by providing complementary treatment when used as add-on therapy.

2. Belgium pubmed.ncbi.nlm.nih.gov

[Canagliflozin (Invokana): kidney SGLT2 cotransporter inhibitor for treating type 2 diabetes]. [2018] Canagliflozin is an inhibitor of sodium-glucose cotransporters type 2 (SGLT2) that are present in renal tubules. This specific insulin-independent mechanism promotes glucosuria, which results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA(1c)). Furthermore, canagliflozin promotes weight loss and lowers arterial (mainly systolic) blood pressure. Its efficacy is decreased in patients with renal insufficiency and the treatment should be stopped if estimated glomerular filtration rate is below 45 ml/min/1.73 m2. Both the efficacy and safety of canagliflozin have been investigated in 24 to 104-week controlled trials versus placebo or versus an active comparator (glimepiride or sitagliptin). The mean reduction in HbA(1c) averages 0.75% when added to other treatments, as compared to placebo. The 100 mg dose is as active as sitagliptin 100 mg while the 300 mg canagliflozin dose is even more efficacious. Adverse events are mostly mycotic genital infections and more rarely mild urinary tract infections. Caution is required in elderly patients and the risk of volume depletion should be checked (hypotension). Hypoglycaemia may occur only in patients already treated with an insulin-secreting agent or insulin. Canagliflozin is commercialized under the trade name Invokana, at the doses of 100 mg and 300 mg once daily, for the treatment of type 2 diabetes.

3. England pubmed.ncbi.nlm.nih.gov

The CANVAS Program: implications of canagliflozin on reducing cardiovascular risk in patients with type 2 diabetes mellitus. [2020] Canagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor that reduces blood glucose, as well as blood pressure, body weight, and albuminuria in patients with type 2 diabetes mellitus (T2DM). In the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, patients with T2DM and high cardiovascular risk treated with canagliflozin had a significantly lower risk of the composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke; hospitalization for heart failure; and renal outcomes, but also a greater risk of lower-limb amputation. Cardiovascular outcomes trials of some other T2DM agents (i.e., empagliflozin, dapagliflozin, liraglutide, semaglutide, albiglutide) have also shown potential cardiovascular and renal benefits. As a result, diabetes treatment guidelines have begun to incorporate consideration of cardiovascular and renal benefits into their treatment recommendations. Antihyperglycemic agents with proven beneficial cardiovascular effects represent a new opportunity for the diabetologist and cardiologist, in the setting of a multidisciplinary approach, to concomitantly improve glycemic control and reduce the risk of cardiovascular events in patients with T2DM. This review briefly discusses the pharmacology of canagliflozin, including clinical and preclinical data; it also describes the effects of canagliflozin on cardiovascular outcomes and side-effects, and compares these effects with other glucose-lowering agents with proven cardiovascular benefits.

4. India pubmed.ncbi.nlm.nih.gov

Acute pancreatitis in the use of canagliflozin: A rare side-effect of the novel therapy for type 2 diabetes mellitus. [2020] Canagliflozin (Invokana) is an innovative treatment for type 2 diabetes mellitus (DM) approved in a new class acknowledged as sodium-glucose co-transporter 2 inhibitors. Acute pancreatitis is a very rare side effect with an incidence

5. England pubmed.ncbi.nlm.nih.gov

Canagliflozin use in patients with renal impairment-Utility of quantitative clinical pharmacology analyses in dose optimization. [2022] Canagliflozin (INVOKANA™) is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). Canagliflozin inhibits renal sodium-glucose co-transporter 2 (SGLT2), thereby, reducing reabsorption of filtered glucose and increasing urinary glucose excretion. Given the mechanism of action of SGLT2 inhibitors, we assessed the interplay between renal function, efficacy (HbA1c reduction), and safety (renal adverse reactions). The focus of this article is to highlight the FDA's quantitative clinical pharmacology analyses that were conducted to support the regulatory decision on dosing in patients with renal impairment (RI). The metrics for assessment of efficacy for T2DM drugs is standard; however, there is no standard method for evaluation of renal effects for diabetes drugs. Therefore, several analyses were conducted to assess the impact of canagliflozin on renal function (as measured by eGFR) based on available data. These analyses provided support for approval of canagliflozin in T2DM patients with baseline eGFR ≥ 45 mL/min/1.73 m(2) , highlighting a data-driven approach to dose optimization. The availability of a relatively rich safety dataset (ie, frequent and early measurements of laboratory markers) in the canagliflozin clinical development program enabled adequate assessment of benefit-risk balance in various patient subgroups based on renal function.

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

Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern. [2022] Canagliflozin (Invokana) is a selective sodium glucose cotransporter-2 (SGLT-2) inhibitor that was first introduced in 2013 for the treatment of type 2 diabetes mellitus (DM). Though not FDA approved yet, its use in type 1 DM has been justified by the fact that its mechanism of action is independent of insulin secretion or action. However, some serious side effects, including severe anion gap metabolic acidosis and euglycemic diabetic ketoacidosis (DKA), have been reported. Prompt identification of the causal association and initiation of appropriate therapy should be instituted for this life threatening condition.

7. England pubmed.ncbi.nlm.nih.gov

Cardiovascular outcomes associated with canagliflozin versus other non-gliflozin antidiabetic drugs: population based cohort study. [2022] To evaluate the cardiovascular safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus, in direct comparisons with DPP-4 inhibitors (DPP-4i), GLP-1 receptor agonists (GLP-1RA), or sulfonylureas, as used in routine practice.

8. England pubmed.ncbi.nlm.nih.gov

The effects of canagliflozin compared to sitagliptin on cardiorespiratory fitness in type 2 diabetes mellitus and heart failure with reduced ejection fraction: The CANA-HF study. [2021] Canagliflozin reduces hospitalizations for heart failure (HF) in type 2 diabetes mellitus (T2DM). Its effect on cardiorespiratory fitness and cardiac function in patients with established HF with reduced ejection fraction (HFrEF) is unknown.

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

Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. [2022] Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM).

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

Evaluation of Bone Mineral Density and Bone Biomarkers in Patients With Type 2 Diabetes Treated With Canagliflozin. [2022] Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM).

11. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of canagliflozin in patients with type 2 diabetes mellitus: pooled analysis of phase 3 study results. [2018] Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed for treating type 2 diabetes mellitus (T2DM).