Doxycycline to Protect Heart Muscle After Heart Attacks

Summary

Current medical treatment allows more people to survive heart attacks than in the past. However, some of the survivors suffer heart disease and require hospitalization later on. The causes behind this heart disease (heart failure) after a heart attack are poorly understood.

Matrix metalloproteinase 2 (MMP-2) is a protein that cuts other proteins into pieces, and is activated in heart muscle when there is a heart attack. MMP-2 causes heart injury when the blood flow to the heart is restored after the attack. Blocking MMP-2 activity is a potential therapy to prevent heart injury under these circumstances. The only MMP-2 inhibiting drug currently approved for clinical use is doxycycline, specifically used to treat periodontitis (gum inflammation) and rosacea (a skin condition). At higher doses doxycycline also acts as an antibiotic for which it has been clinically used for decades.

A previous clinical study found that taking doxycycline twice a day, for one week after a heart attack improved the health of the patients' hearts. The investigators have conducted a similar study in patients that had surgery to replace blocked coronary arteries (blood vessels that feed the heart muscle). These patients took a low dose of doxycycline once a day for 2 days before surgery, on the day of the surgery, and three days after surgery. The participants in this study showed no adverse effects of using doxycycline.

The goal of this study is to see if doxycycline protects the hearts of patients that suffered a heart attack. All patients will receive standard clinical care for their condition, but in addition will take a doxycycline capsule twice a day, or a placebo capsule for 7 days, as soon as possible after being diagnosed with a heart attack. Three months later, the investigators will evaluate the patients by looking at their heart structure using magnetic resonance imaging (MRI). MRI is a powerful tool that allows doctors to see inside the body without surgery or X-ray radiation. The hearts of those patients that received doxycycline are expected to be healthier than those who received placebo.

The investigators plan to promote the use of doxycycline to protect the hearts of patients with heart attacks. If successful, doxycycline could help improve the quality of life of heart attack survivors.

Conditions

• ST Segment Elevation Myocardial Infarction
• Heart Failure

Interventions

DRUG

Placebo

Patients will receive placebo in a loading dose of two capsules initially followed by one capsule every 12 hours for 7 days.

DRUG

Doxycycline Hyclate

Patients will receive doxycycline hyclate in a loading dose of two 100 mg capsules (200 mg total) initially followed by one 100 mg capsule every 12 hours for 7 days.

Sponsors & Collaborators

• Royal Alexandra Hospital

  collaborator OTHER

• University of Alberta

  lead OTHER

Principal Investigators

• Richard Schulz, PhD · Dept. of Pediatrics and Pharmacology, University of Alberta

• Peter Hwang, MD, PhD · Dept. of Medicine, University of Alberta

• Benjamin Tyrrell, MD · Dept. of Medicine, University of Alberta

• Richard Coulden, MD · Dept. of Radiology and Diagnostic Imaging, University of Alberta

• Neil Brass, MD · Dept. of Medicine, University of Alberta

• Raymond Leung, MD · CK Hui Heart Centre, Royal Alexandra Hospital, Edmonton, Alberta.

• Kevin Bainey, MD · Dept. of Medicine, University of Alberta

• Richard Thompson, MD · Dept. of Biomedical Engineering, University of Alberta

• Ian Paterson, MD · Dept. of Medicine, University of Alberta

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-01-06

Primary Completion

2025-07-26

Completion

2025-08-26

Countries

• Canada

Study Locations