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?

This trial tests whether doxycycline, a common antibiotic, can protect the heart after a heart attack. Researchers believe it may prevent heart injury by blocking a protein activated during a heart attack. Participants will take doxycycline or a placebo for 7 days alongside their regular treatment, and their heart health will be assessed three months later. The trial seeks individuals who have experienced a specific type of heart attack called STEMI and were admitted to a hospital in Edmonton, Alberta, within 12 hours of symptoms. If successful, doxycycline might improve the heart health of survivors. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking heart health improvements.

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 there any evidence suggesting that doxycycline is likely to be safe for humans?

Research has shown that doxycycline, the treatment under consideration, has been safely used for conditions like gum inflammation and skin problems. In one study, patients who took doxycycline soon after heart surgery experienced no negative effects, suggesting the drug is generally safe in similar health situations.

However, some studies have raised concerns about using doxycycline for heart attack cases. One study found that doxycycline might interfere with heart healing after an attack. Another study suggested it could increase calcium levels in heart cells, making them more vulnerable.

Given these mixed findings, it is important to note that while doxycycline has been safely used for other conditions, its safety for heart attack treatment remains under investigation. Participants in this trial will receive standard heart attack care, with some also receiving doxycycline to assess if it offers additional heart protection. Always consult a healthcare provider about potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Doxycycline hyclate is unique because it offers a potential new approach to treating heart attacks by targeting inflammation, unlike traditional treatments that mainly focus on restoring blood flow or preventing clot formation. Most current heart attack treatments involve medications like aspirin, beta-blockers, and statins, which have different mechanisms of action. Researchers are excited about doxycycline because it is an antibiotic that might reduce inflammation in heart tissues, which could improve recovery and outcomes after a heart attack. This anti-inflammatory property is what sets doxycycline apart and holds promise for enhancing heart attack care.

What evidence suggests that doxycycline might be an effective treatment for heart attack?

This trial will compare the effects of Doxycycline Hyclate with a placebo in patients who have experienced a heart attack. Research has shown that doxycycline might help protect the heart after a heart attack. In earlier studies, patients who took doxycycline demonstrated better heart health. The drug blocks a protein called MMP-2, which can harm the heart during healing. Animal studies showed that doxycycline reduced heart damage and improved heart function. Although primarily known as an antibiotic, these findings suggest doxycycline could also aid recovery after a heart attack. ^{1 2 3 6 7}

Who Is on the Research Team?

Kevin Bainey, MD

Principal Investigator

Dept. of Medicine, University of Alberta

Neil Brass, 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 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]

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 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 (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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36567466/

UpStreAm doxycycline in ST-eLeVation myocArdial infarction Doxycycline prior to PPCI neither reduced IS acutely or at six months nor attenuated adverse LV remodelling. These data raise safety ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03960411?term=AREA%5BConditionSearch%5D(%22Anterior%20Wall%20Myocardial%20Infarction%22)&rank=7

Effect of Doxycycline on Cardiac Remodelling in STEMI ... Our hypothesis is that a better heart function will be observed in STEMI patients who receive a short period of doxycycline administration post-PCI. Official ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8071362/

The Antibiotic Doxycycline Impairs Cardiac Mitochondrial ... These data suggest that doxycycline increases the baseline cytosolic calcium concentration and makes the cardiomyocyte more vulnerable to ...

4. clinicaltrial.be clinicaltrial.be/en/details/68796

Doxycycline to Protect Heart Muscle After Heart Attacks -... Doxycycline decreases intracellular proteolysis, improves cardiac function, and reduces infarct size in animal models of ischemia-reperfusion ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03508232/doxycycline-to-protect-heart-muscle-after-heart-attacks

Doxycycline to Protect Heart Muscle After Heart Attacks Doxycycline decreases intracellular proteolysis, improves cardiac function, and reduces infarct size in animal models of ischemia-reperfusion ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1443950621010684

the SALVAGE MI Randomised Trial Experimental studies suggest that doxycycline exerts protective effects on myocardial ischaemia-reperfusion injury. We investigated whether doxycycline ...

7. stacks.cdc.gov stacks.cdc.gov/view/cdc/14819/

Lack of association between first myocardial infarction and ... We found that use of erythromycin, tetracycline, or doxycycline during the previous 5 years was not associated with risk for first myocardial infarction. These ...