Comparison of Effects of Atorvastatin Versus Rosuvastatin on Cardiac Function in Heart Failure Patients

NCT ID: NCT05072054

Last Updated: 2021-10-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-16

Study Completion Date

2022-08-31

Brief Summary

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Statins have a protective effect in patients with established heart failure because of their lipid-lowering and pleiotropic effects. There is no randomized controlled trial comparing lipophilic versus hydrophilic statins in these patients (head to head comparison). The best evidence so far is from a meta-analysis in which the authors did an adjusted indirect comparison between lipophilic statins and rosuvastatin and found that lipophilic statins were associated with significantly lower incidence of all-cause mortality, cardiovascular mortality, and hospitalization for worsening heart failure compared to rosuvastatin (hydrophilic statin) among patients with heart failure. So, the investigators plan to conduct a randomized controlled trial comparing the effects of atorvastatin and rosuvastatin on cardiac function in patients with heart failure with reduced ejection fraction.

Detailed Description

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HMG CoA reductase inhibitors or Statins have been widely used for primary prevention and secondary prevention of atherosclerotic cardiovascular disease. Also, the protective effect of statins has been observed in patients with established heart failure because of their lipid-lowering and pleiotropic effects.

Various randomized and non-randomized clinical trials have evaluated statins like Atorvastatin, Rosuvastatin, Simvastatin, Pitavastatin and reported improved clinical outcomes in patients with heart failure with reduced ejection fraction as well as heart failure with preserved ejection fraction. Similar benefits on improved cardiac function, reduced inflammation, and improved mortality have been seen in small randomized controlled trials (RCTs) with Atorvastatin. The two large RCTs - Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA) and Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiac (GISSI-HF) - which compared Rosuvastatin versus placebo, failed to show statistically significant benefits in mortality outcomes in heart failure patients compared to placebo, although CORONA trial did show a significant reduction in hospital admissions but not on mortality.

However, these two large trials only compared one statin i.e rosuvastatin versus placebo; which is a hydrophilic statin. Statin is not a uniform class of drugs. They differ in their pleiotropic effects based on lipophilic nature. There is evidence that lipophilic statins enter cells via passive diffusion and are widely distributed to various tissues including cardiac tissues where it exerts pleiotropic actions whereas uptake of hydrophilic statins is via carrier-mediated mechanisms and is restricted to the liver, thus reduced the capacity of non-lipid effects on extra-hepatic tissues.

Currently, there is no RCT comparing lipophilic statin versus hydrophilic statin (head to head comparison). The best evidence so far is from a meta-analysis which is an adjusted indirect comparison between lipophilic statins and rosuvastatin. They found that lipophilic statins were associated with a significantly lower incidence of all-cause mortality, cardiovascular mortality, and hospitalization for worsening heart failure compared to rosuvastatin (hydrophilic statin) among patients with heart failure. So, the investigators plan to conduct a randomized controlled trial comparing the effects of atorvastatin and rosuvastatin on cardiac function and inflammation in patients with heart failure with reduced ejection fraction.

Conditions

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Heart Failure With Reduced Ejection Fraction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, double-blind clinical study
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Patients will be randomized to two arms in ratio 1:1 using computer-generated random list. Patients, investigator and care provider will be blinded to the treatment group.

Study Groups

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Atorvastatin arm

Tablet Atorvastatin 40mg once daily at bed-time given for 6 months

Group Type EXPERIMENTAL

Atorvastatin Oral Tablet

Intervention Type DRUG

Atorvastatin 40 mg

Rosuvastatin arm

Tablet Rosuvastatin 20mg once daily at bed-time given for 6 months

Group Type ACTIVE_COMPARATOR

Rosuvastatin Oral Tablet

Intervention Type DRUG

Rosuvastatin 20 mg

Interventions

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Atorvastatin Oral Tablet

Atorvastatin 40 mg

Intervention Type DRUG

Rosuvastatin Oral Tablet

Rosuvastatin 20 mg

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Either gender,18-65 years of age
2. Left ventricular ejection fraction \<40% as assessed by 2D echocardiography
3. NYHA class II-III
4. CHF patients currently optimized on standard treatment for at least 1 month before enrolment and on an OPD basis treatment
5. Ready to give written informed consent
6. Willing to comply with the study protocol

Exclusion Criteria

1. Known hypersensitivity to statins
2. NYHA class IV patient
3. Serum creatinine \>3 mg/dl
4. Significant liver disease: SGOT/SGPT \>3 times the upper limit of normal (ULN) or \>2.5 times the ULN in symptomatic patients
5. Patient on an enzyme inducer or inhibitor currently
6. Any malignancy or patient on chemotherapeutic agents
7. Pregnant or lactating females
8. Patients who have participated in another trial within the past 3 months
9. Patient with uncontrolled diabetes mellitus (HbA1c \>7 g%)/ uncontrolled hypertension (BP \>140/90 mmHg despite in ≥3 antihypertensive drugs)
10. Patient with HIV/ HBV / HCV infection
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Indian Council of Medical Research

OTHER_GOV

Sponsor Role collaborator

Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role lead

Responsible Party

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Ashish Kakkar

Associate Professor, Department of Pharmacology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ashish K Kakkar

Role: PRINCIPAL_INVESTIGATOR

Post Graduate Institute of Medical Education and Research, Chandigarh

Locations

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Postgraduate Institute of Medical Education and Research, Chandigarh

Chandigarh, , India

Site Status RECRUITING

Countries

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India

Central Contacts

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Ashish Kakkar, MD, DM

Role: CONTACT

91-172-2755297

Rachna Rohilla, MD

Role: CONTACT

Facility Contacts

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Ashish kakkar, MD, DM

Role: primary

91-172-2755297

Rachna Rohilla, MD

Role: backup

Other Identifiers

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PGIMER-CV-2019

Identifier Type: -

Identifier Source: org_study_id