Effect of Doxycycline on Cardiac Remodelling in STEMI Patients

Effect of Doxycycline on Cardiac Remodelling in Patients With ST-Elevation Myocardial Infarction (STEMI)

Subsequent to the loss of myocardium post-myocardial infarction (MI), the affected ventricle undergoes some dynamic structural and functional changes known as remodeling. Cardiac remodeling progresses into heart failure (HF). In this revolutionized percutaneous coronary intervention (PCI) era, the incidence of post-MI HF due to cardiac remodeling remains high. Current standard therapeutic interventions, for HF, aimed solely at correcting a low cardiac output do not necessarily impede HF progression. Recently, doxycycline was found to have an additional biological effect aside from their antimicrobial actions. From several experimental studies and clinical trials, doxycycline showed MMP inhibition activities that can prevent ventricular remodeling. This study aims to evaluate the role of doxycycline in cardiac remodeling prevention post-MI. Our hypothesis is that a better heart function will be observed in STEMI patients who receive a short period of doxycycline administration post-PCI.

Study Overview

• Status: Unknown
• Conditions: Heart Failure; ST Elevation Myocardial Infarction; Anterior Wall Myocardial Infarction; Remodeling, Ventricular
• Intervention / Treatment: Drug: Doxycycline 100Mg Capsule; Drug: Placebo oral capsule

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta, Indonesia, 11420
    • Recruiting
    • National Cardiovascular Center Harapan Kita Hospital
    • Contact: Bambang Widyantoro, MD, PhD
    • Principal Investigator: Bambang Widyantoro, MD, PhD
    • Sub-Investigator: Felix C Fredy, MD
    • Sub-Investigator: Arief A Subakti, MD
    • Sub-Investigator: Anindita Suputri, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Onset of STEMI <12 hours
• Anterior wall STEMI or Killip grade II-III or LVEF <50%
• Undergoing primary PCI

Exclusion Criteria:

• Signs of infection (clinical judgement plus leukocyte count >15,000)
• STEMI mechanical complication
• Moderate-severe valvular disease
• Allergic to doxycycline
• Refuse to join the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxycycline; Doxycycline 100 mg capsule by mouth every 12 hours for 7 days, administered early after primary PCI	Drug: Doxycycline 100Mg Capsule; Doxycycline capsule; Other Names: Doryx; Doxyhexal; Doxylin
Placebo Comparator: Placebo; Placebo capsule by mouth every 12 hours for 7 days, administered early after primary PCI	Drug: Placebo oral capsule; Capsule manufactured to mimic doxycycline 100 mg capsule; Other Names: Placebo (for Doxycycline)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
high sensitivity-Troponin T	hs-Troponin T in ng/L	12 hours
high sensitivity-CRP	hs-CRP in mg/L	24 hours
NT-pro BNP	NT-pro BNP in pg/ml	5 days
netrophils	absolute amount per micro liters	24 hours
ST2	ST2 in ng/ml	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate	The number of deceased participants	4 months
Heart failure incidence	Evaluating the occurrence of heart failure signs and/or symptoms	4 months
Re-hospitalization rate	The number of patients re-admitted due to heart failure signs and/or symptoms	4 months
Left ventricle function and dimension	Assessed through echocardiography	4 months

Collaborators and Investigators

• Sponsor: Felix Chikita Fredy, MD
• Collaborators: National Cardiovascular Center Harapan Kita Hospital Indonesia
• Investigators: Principal Investigator: Bambang Widyantoro, PhD, Indonesia University

Publications and helpful links

General Publications

• 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.

Helpful Links

• TIPTOP Trial

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2019
• Primary Completion (Anticipated): August 1, 2019
• Study Completion (Anticipated): November 1, 2019

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 20, 2019
• First Posted (Actual): May 23, 2019

Study Record Updates

• Last Update Posted (Actual): August 6, 2019
• Last Update Submitted That Met QC Criteria: August 5, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: STEMI; Doxycycline; Cardiac Remodelling
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Anterior Wall Myocardial Infarction; Ventricular Remodeling; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: 01 (Miami VAHS)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No