The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS (TETHYS Trial)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2013 by Instituto de Cardiologia do Rio Grande do Sul
Sponsor:
Collaborator:
Instituto de Cardiologia de Santa Catarina
Information provided by (Responsible Party):
Instituto de Cardiologia do Rio Grande do Sul
ClinicalTrials.gov Identifier:
NCT01741558
First received: December 3, 2012
Last updated: April 5, 2013
Last verified: April 2013
  Purpose

Experimental studies suggest that anti-inflammatory and immunomodulatory drugs could reduce the inflammatory profile in acute ischemic disease and reduce the area of ​​ischemia. Methotrexate is a drug that has shown promise in ischemic disease in animal studies.


Condition Intervention Phase
Myocardial Infarction
Drug: Methotrexate
Drug: Riboflavin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS: Randomized Double-blind, Placebo-controlled Trial (TETHYS Trial)

Resource links provided by NLM:


Further study details as provided by Instituto de Cardiologia do Rio Grande do Sul:

Primary Outcome Measures:
  • Area under the curve of creatine kinase [ Time Frame: During 72 hours after the infarct ] [ Designated as safety issue: No ]
    The primary end point was the reduction of the size of the infarct as assessed by the area under the curve (AUC) (expressed in arbitrary units) for creatine kinase (CK) during 72 hours after the infarct


Secondary Outcome Measures:
  • Area under the curve for creatine kinase MB fraction and troponin I high sensitive [ Time Frame: During 72 hours after the infarct ] [ Designated as safety issue: No ]
    The primary end point was the reduction of the size of the infarct as assessed by the area under the curve (AUC) (expressed in arbitrary units) for creatine kinase MB fraction(CK-MB) and Troponin I high sensitive during 72 hours after the infarct

  • Compare the peaks of CK, CK-MB and troponin I ultra-sensitive [ Time Frame: During 72 hours after the infarct ] [ Designated as safety issue: No ]
    Compare the peaks of CK, CK-MB and troponin I ultra-sensitive

  • Compare the levels of high-sensitivity C-reactive protein at admission, after 72 hours and after 3 months [ Time Frame: After 72 hours and after 3 months ] [ Designated as safety issue: No ]
    Compare the levels of high-sensitivity C-reactive at admission, after 72 hours and after 3 months

  • Compare the levels of erythrocyte sedimentation rate on admission and after 72 hours [ Time Frame: On admission and after 72 hours ] [ Designated as safety issue: No ]
    Compare the levels of erythrocyte sedimentation rate on admission and after 72 hours

  • Compare B-type natriuretic peptide (BNP) levels on admission, after 72 hours and after 3 months [ Time Frame: On admission, after 72 hours and after 3 months ] [ Designated as safety issue: No ]
    Compare B-type natriuretic peptide (BNP) levels on admission, after 72 hours and after 3 months

  • Compare the "TIMI frame count" of the culprit artery [ Time Frame: On admission ] [ Designated as safety issue: No ]
    Compare the "TIMI frame count" of the culprit artery

  • Compare the Killip score on admission and after 72 hours [ Time Frame: On admission and after 72 hours ] [ Designated as safety issue: No ]
    Compare the Killip score on admission and after 72 hours;

  • Assess ventricular ejection fraction with transthoracic echocardiography during the first 72 hours after 3 months [ Time Frame: During the first 72 hours after 3 months ] [ Designated as safety issue: No ]
    Assess ventricular ejection fraction with transthoracic echocardiography during the first 72 hours after 3 months

  • Assess mortality at 3 months [ Time Frame: At 3 months; ] [ Designated as safety issue: No ]
    Assess mortality at 3 months;

  • Evaluate reinfarction in 3 months [ Time Frame: In 3 months ] [ Designated as safety issue: No ]
    Evaluate reinfarction in 3 months

  • Rate side effects [ Time Frame: In 72 hours ] [ Designated as safety issue: Yes ]
    Evaluation in 72 hours the changes in the levels of hematocrit, hemoglobin, leukocytes and platelets, changes in the levels of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase and prothrombin Time; changes in the levels of plasma creatinine, gastrointestinal effects (oral ulcers, diarrhea, nausea and vomiting), skin changes (rash, pruritus, and alopecia) and pulmonary effects (pneumonitis and pneumonia).


Estimated Enrollment: 80
Study Start Date: April 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Methotrexate
Established treatment associated with methotrexate
Drug: Methotrexate
The treatment group will receive a bolus dose of 0.05 mg/kg of methotrexate before primary angioplasty followed by 0.05 mg/kg per hour for 6 hours
Other Names:
  • Rheumatrex®
  • Trexall®
  • Amethopterin
  • MTX
Placebo Comparator: Placebo (Riboflavin)
Established treatment associated with placebo (riboflavin sodium fosfate 0.1%). We use riboflavin in placebo group to remain the double-blind fashion: methotrexate has a yellow color and riboflavin in that concentration has the same color.
Drug: Riboflavin
We use riboflavin in placebo group to remain the double-blind fashion: methotrexate has a yellow color and riboflavin in that concentration has the same color.
Other Name: Riboflavin

Detailed Description:

Atherosclerosis and ischemic disease have clear association with inflammation. There is an anti-inflammatory action of methotrexate by increasing adenosine. Experimental studies demonstrate reduction of infarct induced in animals treated with methotrexate. We expect a reduction in the area under the curve of creatine kinase (CK), creatine kinase MB fraction (CK-MB) and Troponin I high sensitive, decreased levels of B-type natriuretic peptide (BNP) and improvement in left ventricular ejection fraction.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age over 18 years;
  • Chest pain suggestive of acute myocardial infarction initiated within 12 hours;
  • Electrocardiogram with ST-segment elevation greater than or equal to 0.2 mV in at least 2 contiguous leads;
  • Choice of primary angioplasty

Exclusion Criteria:

  • Prior acute myocardial infarction;
  • Prior heart failure;
  • Angioplasty in the last 3 months;
  • Cardiac arrest or cardiogenic shock;
  • History of renal insufficiency (serum creatinine greater than 2.0 mg/dl);
  • History of alcohol abuse (consumption equal to or greater than 20 drinks per week);
  • Illicit drug use;
  • Evidence of rheumatoid arthritis;
  • Neoplasia;
  • Infectious diseases;
  • Prior anemia (hematocrit below 30%);
  • Use of anti-inflammatory hormonal or non-hormonal last week;
  • Xanthines excessive consumption (more than two and a half cups of coffee or two and a half mate gourds);
  • Pregnancy;
  • Disagreement with the term of consent;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01741558

Contacts
Contact: Daniel M. Moreira, MSc. 554884175590 danielmedeirosmoreira@gmail.com

Locations
Brazil
Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia Not yet recruiting
Porto Alegre, Rio Grande do Sul, Brazil, 90620001
Contact: Daniel M. Moreira, MD. MSc.    554884175590    danielmedeirosmoreira@gmail.com   
Principal Investigator: Daniel M. Moreira, MD. MSc.         
Sub-Investigator: Carlos AM Gottschall, MD MSc PhD         
Instituto de Cardiologia de Santa Catarina Not yet recruiting
São José, Santa Catarina, Brazil, 88103901
Contact: Daniel M. Moreira, MD. MSc    554884175590    danielmedeirosmoreira@gmail.com   
Sub-Investigator: Maria E. Lueneberg, MD.         
Principal Investigator: Daniel M. Moreira, MD. MSc.         
Sub-Investigator: Roberto L. da Silva, MD.         
Sub-Investigator: Tammuz Fattah, MD.         
Sponsors and Collaborators
Instituto de Cardiologia do Rio Grande do Sul
Instituto de Cardiologia de Santa Catarina
Investigators
Study Chair: Daniel M. Moreira, MD. MSc. Instituto de Cardiologia do Rio Grande do Sul
Study Director: Daniel M. Moreira, MD. MSc Instituto de Cardiologia do Rio Grande do Sul
Principal Investigator: Daniel M. Moreira, MD. MSc. Instituto de Cardiologia do Rio Grande do Sul
Study Director: Carlos AM Gottschall, MD MSc PhD Instituto de Cardiologia do Rio Grande do Sul
Study Director: Maria E. Lueneberg, MD. Instituto de Cardiologia de Santa Catarina
Study Director: Roberto L. da Silva, MD. Instituto de Cardiologia de Santa Catarina
Study Director: Tammuz Fattah, MD. Instituto de Cardiologia de Santa Catarina
  More Information

No publications provided

Responsible Party: Instituto de Cardiologia do Rio Grande do Sul
ClinicalTrials.gov Identifier: NCT01741558     History of Changes
Other Study ID Numbers: UP 4747/12, CAAE 04482712.3.0000.5333
Study First Received: December 3, 2012
Last Updated: April 5, 2013
Health Authority: Brazil: Ethics Committee

Keywords provided by Instituto de Cardiologia do Rio Grande do Sul:
Myocardial Ischemia
Myocardial Infarction
Methotrexate
Inflammation
Anti-Inflammatory Agents
Inflammation Mediators

Additional relevant MeSH terms:
Riboflavin
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Anti-Inflammatory Agents
Methotrexate
Therapeutic Uses
Pharmacologic Actions
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Vitamin B Complex

ClinicalTrials.gov processed this record on August 21, 2014