Doxycycline to Protect Heart Muscle After Heart Attacks

NCT03508232 | Completed Phase 2

• 1 other identifier: DOXY-STEMI
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

Brief 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

Outcome Measures

Primary Outcomes (1)

• Left ventricular end-systolic volume index (LVESVi)

  Left ventricular end-systolic volume index (LVESVi) measured by magnetic resonance imaging (MRI) at 3 months post intervention

  3 months post intervention

Secondary Outcomes (4)

• Composite endpoint of mortality and hospital admission due to re-infarction, heart failure, or stroke

  3 months and one year post intervention

• Left ventricular ejection fraction (LVEF)

  3 months post intervention

• Left ventricular end-diastolic volume index (LVEDVi)

  3 months post intervention

• Infarct size

  3 months post intervention

Study Arms (2)

Placebo control

PLACEBO COMPARATOR

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

Drug: Doxycycline Hyclate

Doxycycline hyclate

EXPERIMENTAL

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

Drug: Placebo

Interventions

Placebo DRUG

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

Doxycycline hyclate

Doxycycline Hyclate DRUG

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.

Also known as: Doxycycline

Placebo control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• + year old
• Diagnosis of acute ST-elevation myocardial infarction (STEMI)
• Primary STEMI
• Symptom onset of less than 12 hours
• Admitted to the Royal Alexandra Hospital in Edmonton, Alberta

You may not qualify if:

• Low risk inferior STEMI (total ST elevation plus depression \<4mm)
• Cardiogenic shock
• Use of thrombolytics
• Prior history of myocardial infarction or heart failure
• Known hypersensitivity to tetracyclines
• Any concurrent medical condition expected to reduce life expectancy to \<1 year
• Symptom onset to treatment (loading dose) time longer than 24 hours
• Poor renal function (eGFR\<30 mL/min/1.73m2) or other contraindications to MRI (claustrophobia, pregnancy, PPM/ICD, sub-arachnoid clips, retained ocular foreign body)

Sponsors & Collaborators

• University of Alberta: lead
• Royal Alexandra Hospital: collaborator

Study Sites (1)

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

Related Publications (5)

• Schulz R. Intracellular targets of matrix metalloproteinase-2 in cardiac disease: rationale and therapeutic approaches. Annu Rev Pharmacol Toxicol. 2007;47:211-42. doi: 10.1146/annurev.pharmtox.47.120505.105230.

  PMID: 17129183 BACKGROUND

• Cheung PY, Sawicki G, Wozniak M, Wang W, Radomski MW, Schulz R. Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart. Circulation. 2000 Apr 18;101(15):1833-9. doi: 10.1161/01.cir.101.15.1833.

  PMID: 10769285 BACKGROUND

• Villarreal FJ, Griffin M, Omens J, Dillmann W, Nguyen J, Covell J. Early short-term treatment with doxycycline modulates postinfarction left ventricular remodeling. Circulation. 2003 Sep 23;108(12):1487-92. doi: 10.1161/01.CIR.0000089090.05757.34. Epub 2003 Sep 2.

  PMID: 12952845 BACKGROUND

• Schulze CJ, Castro MM, Kandasamy AD, Cena J, Bryden C, Wang SH, Koshal A, Tsuyuki RT, Finegan BA, Schulz R. Doxycycline reduces cardiac matrix metalloproteinase-2 activity but does not ameliorate myocardial dysfunction during reperfusion in coronary artery bypass patients undergoing cardiopulmonary bypass. Crit Care Med. 2013 Nov;41(11):2512-20. doi: 10.1097/CCM.0b013e318292373c.

  PMID: 23928836 BACKGROUND

• Cerisano G, Buonamici P, Valenti R, Sciagra R, Raspanti S, Santini A, Carrabba N, Dovellini EV, Romito R, Pupi A, Colonna P, Antoniucci D. Early short-term doxycycline therapy in patients with acute myocardial infarction and left ventricular dysfunction to prevent the ominous progression to adverse remodelling: the TIPTOP trial. Eur Heart J. 2014 Jan;35(3):184-91. doi: 10.1093/eurheartj/eht420. Epub 2013 Oct 8.

  PMID: 24104875 BACKGROUND

MeSH Terms

Conditions

ST Elevation Myocardial Infarction; Heart Failure

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Richard Schulz, PhD

  Dept. of Pediatrics and Pharmacology, University of Alberta

  STUDY CHAIR

• Peter Hwang, MD, PhD

  Dept. of Medicine, University of Alberta

  STUDY DIRECTOR

• Benjamin Tyrrell, MD

  Dept. of Medicine, University of Alberta

  STUDY DIRECTOR

• Richard Coulden, MD

  Dept. of Radiology and Diagnostic Imaging, University of Alberta

  PRINCIPAL INVESTIGATOR

• Neil Brass, MD

  Dept. of Medicine, University of Alberta

  PRINCIPAL INVESTIGATOR

• Raymond Leung, MD

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

  PRINCIPAL INVESTIGATOR

• Kevin Bainey, MD

  Dept. of Medicine, University of Alberta

  PRINCIPAL INVESTIGATOR

• Richard Thompson, MD

  Dept. of Biomedical Engineering, University of Alberta

  PRINCIPAL INVESTIGATOR

• Ian Paterson, MD

  Dept. of Medicine, University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinding. Randomization will be done prior to the study and with binary encoding, for further blinding. Drug randomization (placebo or doxycycline) will be done by the Drug Development and Innovation Centre in the Faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta, with 50% allocated in the Placebo Control Group and 50% in the Doxycycline Group. The coding list will be generated and kept sealed by the PI. Patients will be randomized during recruitment, following a previously generated list with 50% of patients allocated to each group.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blinded, placebo-controlled study

Study Record Dates

• First Submitted: April 16, 2018
• First Posted: April 25, 2018
• Study Start: January 6, 2020
• Primary Completion: July 26, 2025
• Study Completion: August 26, 2025
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)