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

Primary Purpose

Myocardial Infarction

Status
Unknown status
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Methotrexate
Riboflavin
Sponsored by
Instituto de Cardiologia do Rio Grande do Sul
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myocardial Infarction focused on measuring Myocardial Ischemia, Myocardial Infarction, Methotrexate, Inflammation, Anti-Inflammatory Agents, Inflammation Mediators

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

  • Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia
  • Instituto de Cardiologia de Santa Catarina

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Methotrexate

Placebo (Riboflavin)

Arm Description

Established treatment associated with methotrexate

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.

Outcomes

Primary Outcome Measures

Area under the curve of creatine kinase
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
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
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
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
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
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
Compare the "TIMI frame count" of the culprit artery
Compare the Killip score on admission and after 72 hours
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
Assess ventricular ejection fraction with transthoracic echocardiography during the first 72 hours after 3 months
Assess mortality at 3 months
Assess mortality at 3 months;
Evaluate reinfarction in 3 months
Evaluate reinfarction in 3 months
Rate side effects
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).

Full Information

First Posted
December 3, 2012
Last Updated
April 5, 2013
Sponsor
Instituto de Cardiologia do Rio Grande do Sul
Collaborators
Instituto de Cardiologia de Santa Catarina
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1. Study Identification

Unique Protocol Identification Number
NCT01741558
Brief Title
The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS (TETHYS Trial)
Acronym
TETHYS
Official Title
The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS: Randomized Double-blind, Placebo-controlled Trial (TETHYS Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2013
Overall Recruitment Status
Unknown status
Study Start Date
April 2013 (undefined)
Primary Completion Date
August 2014 (Anticipated)
Study Completion Date
December 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instituto de Cardiologia do Rio Grande do Sul
Collaborators
Instituto de Cardiologia de Santa Catarina

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction
Keywords
Myocardial Ischemia, Myocardial Infarction, Methotrexate, Inflammation, Anti-Inflammatory Agents, Inflammation Mediators

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Methotrexate
Arm Type
Experimental
Arm Description
Established treatment associated with methotrexate
Arm Title
Placebo (Riboflavin)
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
Rheumatrex®, Trexall®, Amethopterin, MTX
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Riboflavin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Area under the curve of creatine kinase
Description
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
Time Frame
During 72 hours after the infarct
Secondary Outcome Measure Information:
Title
Area under the curve for creatine kinase MB fraction and troponin I high sensitive
Description
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
Time Frame
During 72 hours after the infarct
Title
Compare the peaks of CK, CK-MB and troponin I ultra-sensitive
Description
Compare the peaks of CK, CK-MB and troponin I ultra-sensitive
Time Frame
During 72 hours after the infarct
Title
Compare the levels of high-sensitivity C-reactive protein at admission, after 72 hours and after 3 months
Description
Compare the levels of high-sensitivity C-reactive at admission, after 72 hours and after 3 months
Time Frame
After 72 hours and after 3 months
Title
Compare the levels of erythrocyte sedimentation rate on admission and after 72 hours
Description
Compare the levels of erythrocyte sedimentation rate on admission and after 72 hours
Time Frame
On admission and after 72 hours
Title
Compare B-type natriuretic peptide (BNP) levels on admission, after 72 hours and after 3 months
Description
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
Title
Compare the "TIMI frame count" of the culprit artery
Description
Compare the "TIMI frame count" of the culprit artery
Time Frame
On admission
Title
Compare the Killip score on admission and after 72 hours
Description
Compare the Killip score on admission and after 72 hours;
Time Frame
On admission and after 72 hours
Title
Assess ventricular ejection fraction with transthoracic echocardiography during the first 72 hours after 3 months
Description
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
Title
Assess mortality at 3 months
Description
Assess mortality at 3 months;
Time Frame
At 3 months;
Title
Evaluate reinfarction in 3 months
Description
Evaluate reinfarction in 3 months
Time Frame
In 3 months
Title
Rate side effects
Description
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).
Time Frame
In 72 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daniel M. Moreira, MSc.
Phone
554884175590
Email
danielmedeirosmoreira@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel M. Moreira, MD. MSc.
Organizational Affiliation
Instituto de Cardiologia do Rio Grande do Sul
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Daniel M. Moreira, MD. MSc
Organizational Affiliation
Instituto de Cardiologia do Rio Grande do Sul
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Daniel M. Moreira, MD. MSc.
Organizational Affiliation
Instituto de Cardiologia do Rio Grande do Sul
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Carlos AM Gottschall, MD MSc PhD
Organizational Affiliation
Instituto de Cardiologia do Rio Grande do Sul
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Maria E. Lueneberg, MD.
Organizational Affiliation
Instituto de Cardiologia de Santa Catarina
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Roberto L. da Silva, MD.
Organizational Affiliation
Instituto de Cardiologia de Santa Catarina
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Tammuz Fattah, MD.
Organizational Affiliation
Instituto de Cardiologia de Santa Catarina
Official's Role
Study Director
Facility Information:
Facility Name
Instituto de Cardiologia do Rio Grande do Sul / Fundação Universitária de Cardiologia
City
Porto Alegre
State/Province
Rio Grande do Sul
ZIP/Postal Code
90620001
Country
Brazil
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel M. Moreira, MD. MSc.
Phone
554884175590
Email
danielmedeirosmoreira@gmail.com
First Name & Middle Initial & Last Name & Degree
Daniel M. Moreira, MD. MSc.
First Name & Middle Initial & Last Name & Degree
Carlos AM Gottschall, MD MSc PhD
Facility Name
Instituto de Cardiologia de Santa Catarina
City
São José
State/Province
Santa Catarina
ZIP/Postal Code
88103901
Country
Brazil
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel M. Moreira, MD. MSc
Phone
554884175590
Email
danielmedeirosmoreira@gmail.com
First Name & Middle Initial & Last Name & Degree
Maria E. Lueneberg, MD.
First Name & Middle Initial & Last Name & Degree
Daniel M. Moreira, MD. MSc.
First Name & Middle Initial & Last Name & Degree
Roberto L. da Silva, MD.
First Name & Middle Initial & Last Name & Degree
Tammuz Fattah, MD.

12. IPD Sharing Statement

Citations:
PubMed Identifier
28325070
Citation
Moreira DM, Lueneberg ME, da Silva RL, Fattah T, Gottschall CAM. MethotrexaTE THerapy in ST-Segment Elevation MYocardial InfarctionS: A Randomized Double-Blind, Placebo-Controlled Trial (TETHYS Trial). J Cardiovasc Pharmacol Ther. 2017 Nov;22(6):538-545. doi: 10.1177/1074248417699884. Epub 2017 Mar 22.
Results Reference
derived

Learn more about this trial

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

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