Doxycycline for Heart Attack

Overseen By Richard Schulz, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alberta

Must not be taking: Thrombolytics, Tetracyclines

Disqualifiers: Prior heart attack, Heart failure, others

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

Compensation: Varies

Number of Visits: 3

Duration: 1 week

170 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It mentions that all patients will receive standard clinical care along with the trial medication, so it's best to discuss your specific medications with the trial team.

Is doxycycline safe for humans?

Doxycycline is generally safe for humans, but it can cause gastrointestinal issues like nausea and abdominal pain. Enteric-coated versions, like Doryx, tend to have fewer side effects compared to other forms like Vibramycin. Other safety concerns include tooth development issues in children, sensitivity to sunlight, and rare effects like high blood pressure. ^{1 2 3 4 5}

How does the drug Doxycycline Hyclate differ from other treatments for heart attacks?

Doxycycline Hyclate is unique because it is primarily known for its broad-spectrum antimicrobial and antiviral properties, which are not typical for heart attack treatments. Additionally, it has been shown to have a favorable effect on the immune response and is available in an enteric-coated form to reduce gastrointestinal side effects, which may offer a novel approach compared to standard heart attack therapies. ^{3 4 5 6 7}

What data supports the effectiveness of the drug Doxycycline for heart attack?

There is no direct evidence from the provided research that supports the effectiveness of Doxycycline for treating heart attacks. However, Doxycycline has shown effectiveness in treating bacterial infections and has potential antiviral properties, which might suggest some broader therapeutic applications. ^{1 3 5 6 8}

Who Is on the Research Team?

Neil Brass, MD

Principal Investigator

Dept. of Medicine, University of Alberta

Kevin Bainey, MD

Principal Investigator

Dept. of Medicine, University of Alberta

Raymond Leung, MD

Principal Investigator

CK Hui Heart Centre, Royal Alexandra Hospital, Edmonton, Alberta.

Richard Schulz, PhD

Principal Investigator

Dept. of Pediatrics and Pharmacology, University of Alberta

Peter Hwang, MD, PhD

Principal Investigator

Dept. of Medicine, University of Alberta

Benjamin Tyrrell, MD

Principal Investigator

Dept. of Medicine, University of Alberta

Richard Coulden, MD

Principal Investigator

Dept. of Radiology and Diagnostic Imaging, University of Alberta

Richard Thompson, MD

Principal Investigator

Dept. of Biomedical Engineering, University of Alberta

Ian Paterson, MD

Principal Investigator

Dept. of Medicine, University of Alberta

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had a recent severe heart attack (STEMI) and are admitted to the Royal Alexandra Hospital in Edmonton. It's not for those with low-risk conditions, previous heart attacks or failure, allergies to tetracyclines, life expectancy less than a year due to other diseases, poor kidney function, or factors that prevent MRI use.

Inclusion Criteria

Admitted to the Royal Alexandra Hospital in Edmonton, Alberta

I had a major heart attack.

I have been diagnosed with a severe type of heart attack.

Exclusion Criteria

I have experienced a severe heart condition known as cardiogenic shock.

My heart attack was classified as low risk.

I have poor kidney function or cannot undergo an MRI due to other health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive doxycycline or placebo capsules twice a day for 7 days

1 week

Daily administration (self-administered)

Follow-up

Participants are monitored for safety and effectiveness after treatment using MRI and echocardiography

3 months

2 visits (in-person) at 3 months and 1 year

Long-term follow-up

Participants are monitored for mortality and hospital admission due to cardiac events

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Doxycycline Hyclate
• Placebo

Trial Overview The study tests if doxycycline can protect the heart after an attack. Participants will take either doxycycline or a placebo twice daily for seven days post-heart attack. Their heart health will be assessed via MRI three months later to see if doxycycline improves their condition.

How Is the Trial Designed?

Group I: Doxycycline hyclate Experimental Treatment 1 Intervention

Two 100mg doxycycline capsules (200 mg) p.o. upon enrollment, followed by one 100 mg capsule p.o. every 12 hours for 7 days

Group II: Placebo control Placebo Group 1 Intervention

Two placebo capsules upon enrollment, followed by one placebo capsule p.o. every 12 hours for 7 days

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

Approved in United States as Doxycycline Hyclate for:

• Acne
• Malaria
• Skin infections
• Sexually transmitted infections
• Lyme disease

Approved in European Union as Doxycycline Hyclate for:

• Acne
• Malaria
• Skin infections
• Sexually transmitted infections
• Lyme disease

Approved in Canada as Doxycycline Hyclate for:

• Acne
• Malaria
• Skin infections
• Sexually transmitted infections
• Lyme disease

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Royal Alexandra Hospital

Collaborator

Trials

20

Recruited

9,300+

Published Research Related to This Trial

Doxycycline (Dox) demonstrated significant antiviral activity against vesicular stomatitis virus (VSV) in cultured H1299 cells, inhibiting viral replication in a dose-dependent manner at concentrations of 1.0-2.0 μg/ml.

The antiviral effect of Dox occurs during the early to mid-stages of VSV infection, indicating that it does not affect the virus's ability to enter cells, suggesting potential for Dox in treating viral infections beyond its known antibacterial properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiviral activity of doxycycline against vesicular stomatitis virus in vitro. Wu, ZC., Wang, X., Wei, JC., et al.[2015]

In a study involving 98 healthy subjects, Doryx (enteric-coated doxycycline) was found to cause significantly fewer gastrointestinal side effects, such as nausea and abdominal discomfort, compared to Vibramycin (doxycycline powder).

While Doryx did lead to some reports of nausea compared to placebo, it overall had a better safety profile regarding gastrointestinal symptoms than Vibramycin, making it a preferable option for patients concerned about these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, multiple-dose, placebo-controlled, cross-over study to compare the incidence of gastrointestinal complaints in healthy subjects given Doryx R and Vibramycin R. Berger, RS.[2019]

In a study involving 111 healthy volunteers, enteric-coated doxycycline hyclate pellets in capsules were found to cause significantly fewer gastrointestinal adverse reactions compared to doxycycline monohydrate tablets, with only 43% of participants reporting side effects versus 66% for monohydrate.

The new formulation demonstrated improved tolerability, particularly reducing incidents of abdominal pain, nausea, and vomiting, making it a safer option for patients requiring doxycycline therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enteric Coating Reduces Upper Gastrointestinal Adverse Reactions to Doxycycline. Järvinen, A., Nykänen, S., Paasiniemi, L., et al.[2018]

In a study of 19 patients with endocarditis who had not responded to previous treatments, high doses of oral doxycycline (15-20 mg/kg/day) led to complete cures in 11 patients and significant improvements in one patient.

The results suggest that high-dose doxycycline can be an effective treatment option for endocarditis, especially for patients resistant to traditional bactericidal antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Endocarditis therapy with high doses of oral doxycycline: Part II: Clinical study (author's transl)]. Wagner, P., Marget, W.[2013]

In a study of 33 patients with bacterial infections, doxycycline administered as a drip infusion showed a good clinical effect, with 76% of patients achieving very good or good results.

Bacteriological tests indicated that 58% of tetracycline-sensitive bacteria were eliminated, and toleration of the treatment was excellent across all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of the clinical efficacy and tolerance of vibramycin dry fill infusions]. Weber, FW.[2013]

Doxycycline hyclate (DH) has a favorable safety profile, especially in its delayed-release form (Doryx), compared to the standard powder form (Vibramycin), making it a safer option for treating conditions like acne and rosacea.

Despite historical safety concerns associated with tetracyclines, including gastrointestinal issues and effects on tooth development, subantimicrobial dosing of DH has shown to be effective and safe for acne treatment, supporting its continued use in dermatology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use and safety of doxycycline hyclate and other second-generation tetracyclines. Sloan, B., Scheinfeld, N.[2022]

Doxycycline is an effective antibiotic for treating various infections, particularly respiratory tract diseases like pneumonia, as demonstrated in a study involving 49 patients.

The drug shows good safety and compatibility, especially in children, and achieves effective serum levels when administered at a dose of 4 mg/kg in two injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical and pharmacokinetic researches of doxycyclin vibravenös in childhood (author's transl)]. Weingärtner, L., Straube, D., Baum, W., et al.[2013]

Doxycycline treatment in mice resulted in a significant increase in heart transplant survival duration, extending it from 14.5 days in untreated animals to 18.8 days, indicating a potential immunomodulatory effect.

While doxycycline moderately decreased the immune response to sheep erythrocytes, it did not inhibit the overall production of antibodies, suggesting that its effects on immunity may be limited and context-dependent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of doxycycline on immune response in mice. Bellahsene, A., Forsgren, A.[2021]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Antiviral activity of doxycycline against vesicular stomatitis virus in vitro. [2015]

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

A double-blind, multiple-dose, placebo-controlled, cross-over study to compare the incidence of gastrointestinal complaints in healthy subjects given Doryx R and Vibramycin R. [2019]

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

Enteric Coating Reduces Upper Gastrointestinal Adverse Reactions to Doxycycline. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

[Endocarditis therapy with high doses of oral doxycycline: Part II: Clinical study (author's transl)]. [2013]

5. Germany pubmed.ncbi.nlm.nih.gov

[Evaluation of the clinical efficacy and tolerance of vibramycin dry fill infusions]. [2013]

6. England pubmed.ncbi.nlm.nih.gov

The use and safety of doxycycline hyclate and other second-generation tetracyclines. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

[Clinical and pharmacokinetic researches of doxycyclin vibravenös in childhood (author's transl)]. [2013]

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

Effect of doxycycline on immune response in mice. [2021]