The purpose of the trial is to assess the efficacy and safety of tirzepatide to dulaglutide in participants with type 2 diabetes and increased cardiovascular risk.

Elegibilidad

Edad mínima: 40 YearsSexo: ALL

Criterios de inclusión

Men or women at least 40 years old with a diagnosis of type 2 diabetes
Established cardiovascular disease, including at least 1 of the following:
Coronary artery disease (CAD) with any of the following:
Documented history of spontaneous myocardial infarction (MI)
≥50% stenosis in 1 or more major coronary arteries, determined by invasive angiography
≥50% stenosis in 2 or more major coronary arteries, determined by computed tomography coronary angiography (CTCA)
History of surgical or percutaneous coronary revascularization procedure
Cerebrovascular disease - any of the following:
Documented history of ischemic stroke
Carotid arterial disease with ≥50% stenosis, documented by carotid ultrasound, magnetic resonance imaging (MRI), or angiography
Carotid stenting or surgical revascularization
Peripheral arterial disease with either of the following:
Intermittent claudication and ankle-brachial index \<0.9
Prior nontraumatic amputation or peripheral vascular procedure (eg, stenting or surgical revascularization), due to peripheral arterial ischemia
Note: Supporting medical documentation is required in all instances
HbA1c ≥7% (≥53 mmol/mol) and ≤10.5% (≤91.3 mmol/mol) based on central laboratory assessment at screening
Body mass index (BMI) ≥25 kg/m2
At the time of signing the informed consent: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials.
Male patients: Men, regardless of their fertility status, with nonpregnant women of childbearing potential (WOCBP) partners must agree to either remain abstinent (if this is their preferred and usual lifestyle) or use condoms, as well as 1 additional highly effective (less than 1% failure rate) method of contraception (such as combination oral contraceptives, implanted contraceptives, or intrauterine devices) or effective method of contraception (such as diaphragms with spermicide or cervical sponges) for the duration of the study and until their plasma concentrations are below the level that could result in a relevant potential exposure to a possible fetus, predicted to be 90 days following the last dose of study drug.
Men and their partners may choose to use a double-barrier method of contraception. (Barrier protection methods without concomitant use of a spermicide are not an effective or acceptable method of contraception. Thus, each barrier method must include use of a spermicide. It should be noted, however, that the use of male and female condoms as a double barrier method is not considered acceptable due to the high failure rate when these barrier methods are combined).
Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods), declaration of abstinence just for the duration of a trial, and withdrawal are not acceptable methods of contraception.
Men with pregnant partners should use condoms during intercourse for the duration of the study and until the end of the estimated relevant potential exposure in WOCBP (90 days). Men should refrain from sperm donation for the duration of the study and until their plasma concentrations are below the level that could result in a relevant potential exposure to a possible fetus, predicted to be 90 days following the last dose of study drug. Men who are in exclusively same-sex relationships (as their preferred and usual lifestyle) are not required to use contraception.
Female patients: Women of childbearing potential who are abstinent (if this is complete abstinence, as their preferred and usual lifestyle) or in a same-sex relationship (as part of their preferred and usual lifestyle) must agree to either remain abstinent or stay in a same-sex relationship without sexual relationships with males. Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods), declaration of abstinence just for the duration of a trial, and withdrawal are not acceptable methods of contraception. Otherwise, WOCBP participating must agree to use 2 forms of effective contraception, where at least 1 form is highly effective (less than 1% failure rate), for the entirety of the study. Contraception must continue following completion of study drug administration for the entirety of the study and for 30 days thereafter.
WOCBP participating must test negative for pregnancy prior to initiation of treatment as indicated by a negative serum pregnancy test at the screening visit followed by a negative urine pregnancy test within 24 hours prior to exposure.
Two forms of effective contraception, where at least 1 form is highly effective, (such as combination oral contraceptives, implanted contraceptives, or intrauterine devices) will be used. Effective contraception (such as male or female condoms with spermicide, diaphragms with spermicide, or cervical sponges) may be used as the second therapy. Barrier protection methods without concomitant use of a spermicide are not a reliable or acceptable method. Thus, each barrier method must include use of a spermicide (ie, condom with spermicide, diaphragm with spermicide, or female condom with spermicide). It should be noted that the use of male and female condoms as a double barrier method is not considered acceptable due to the high failure rate when these methods are combined.
Women not of childbearing potential may participate and include those who are:
infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as mullerian agenesis, or
postmenopausal - defined as either: A woman at least 40 years of age with an intact uterus, not on hormone therapy, who has cessation of menses for at least 1 year without an alternative medical cause, AND a follicle-stimulating hormone \>40 mIU/mL; or ii. A woman 55 or older not on hormone therapy, who has had at least 12 months of spontaneous amenorrhea; or A woman at least 55 years of age with a diagnosis of menopause prior to starting hormone replacement therapy.
In the investigator's opinion, are well motivated, capable, and willing to:
learn how to self-inject treatment (tirzepatide or dulaglutide), as required for this protocol (visually impaired persons who are not able to perform the injections must have the assistance of a sighted individual trained to inject the study drug; persons with physical limitations who are not able to perform the injections must have the assistance of an individual trained to inject the study drug),
inject study drug weekly,
have a sufficient understanding of 1 of the provided languages of the country such that they will be able to complete the patient questionnaires, and
make themselves available for the duration of the study, and who will comply with the required study visits.
Capable of giving signed informed consent

Criterios de exclusión

Have type 1 diabetes mellitus
Have uncontrolled diabetes requiring immediate therapy (such as diabetic ketoacidosis) at screening or randomization, in the judgment of the physician
Have had 1 or more events of severe hypoglycemia and/or 1 or more events of hypoglycemia unawareness within 6 months prior to screening
Are currently planning treatment for diabetic retinopathy and/or macular edema.
Have been hospitalized for congestive heart failure (CHF) within 2 months prior to screening
Have chronic New York Heart Association Functional Classification IV CHF
Are currently planning a coronary, carotid, or peripheral artery revascularization
Had chronic or acute pancreatitis any time prior to screening, irrespective of etiology
Have a known clinically significant gastric emptying abnormality such as severe gastroparesis or gastric outlet obstruction, or have undergone or currently planning any gastric bypass (bariatric) surgery or restrictive bariatric surgery
Have acute or chronic hepatitis, signs or symptoms of any other liver disease, an alanine aminotransferase (ALT) level ≥3 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory (Note: Patients with nonalcoholic fatty liver disease are eligible to participate if their ALT level is \<3 times the ULN for the reference range)
Have known chronic severe renal failure (defined as a known estimated glomerular filtration rate (eGFR) \<15 mL/minute/1.73 m2) or are on chronic dialysis
Have evidence of a significant, uncontrolled endocrine abnormality (eg, thyrotoxicosis or adrenal crises)
Have a family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (MTC) or personal history of nonfamilial MTC
Have a serum calcitonin level at screening of: (based on central laboratory results)
≥20 ng/L at Visit 1, if eGFR ≥60 mL/min/1.73 m2, or
≥35 ng/L at Visit 1, if eGFR \<60 mL/min/1.73 m2
Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years. An exception for this criterion is basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer
Have a history of any other condition (such as known drug or alcohol abuse or psychiatric disorder) that, in the opinion of the investigator, may preclude the patient from following and completing the protocol
Have had a transplanted organ (corneal transplants \[keratoplasty\] allowed) or awaiting an organ transplant
Have any other condition (eg, hypersensitivity) that is a contraindication to any incretin or glucagon-like peptide-1 (GLP-1) receptor agonist (RA)
Have had an MI, percutaneous coronary revascularization procedure, ischemic stroke, carotid stenting or surgical revascularization, nontraumatic amputation, or peripheral vascular procedure (eg, stenting or surgical revascularization) less than 60 days prior to screening
Have had coronary artery bypass graft surgery less than 5 years prior to screening
Have had a blood transfusion or severe blood loss within 90 days prior to screening or have known hematological conditions that may interfere with HbA1c measurement
Treatment with GLP-1 RA or pramlintide, in a period of 3 months prior to Visit 1
Discontinuation of GLP-1 RA or pramlintide, due to intolerability any time prior to Visit 1
Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study
Have participated within the last 30 days in a clinical trial involving an investigational product. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed
Have previously completed or withdrawn from this study or randomized into any other study investigating tirzepatide

Ubicaciones

Instituto de Investigaciones Clínicas Bahia Blanca

Bahía Blanca, Buenos Aires, Argentina

Organizacion Medica de Investigacion

CABA, Buenos Aires, Argentina

CEDIC

CABA, Buenos Aires, Argentina

Stat Research S.A.

Capital Federal, Buenos Aires, Argentina

Centro de Investigaciones Metabólicas (CINME)

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

Instituto de Investigaciones Clínicas Mar del Plata

Mar del Plata, Buenos Aires, Argentina

DIM Clínica Privada

Ramos Mejía, Buenos Aires, Argentina

Go Centro Medico San Nicolás

San Nicolás de los Arroyos, Buenos Aires, Argentina

Instituto de Investigaciones Clinicas Zarate

Zárate, Buenos Aires, Argentina

Centro Médico Viamonte

Buenos Aires, Buenos Aires F.D., Argentina

Mautalen Salud e Investigación

Buenos Aires, Buenos Aires F.D., Argentina

Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada

Buenos Aires, Buenos Aires F.D., Argentina

CEMEDIAB

C.a.b.a., Buenos Aires F.D., Argentina

Centro Medico Privado CEMAIC

Capital, Córdoba Province, Argentina

Centro Medico Privado San Vicente Diabetes

Córdoba, Córdoba Province, Argentina

Instituto Médico Catamarca IMEC

Rosario, Santa Fe Province, Argentina

Instituto Médico Fundación Grupo Colaborativo Rosario Investigación y Prevención Medica

Rosario, Santa Fe Province, Argentina

Instituto de Investigaciones Clinicas Rosario

Rosario, Santa Fe Province, Argentina

Centro de Investigaciones Médicas Tucuman

SAN M. de Tucuman, Tucumán Province, Argentina

Clínica Mayo de Urgencias Médicas Cruz Blanca S.R.L

San Miguel de Tucumán, Tucumán Province, Argentina

Investigaciones Clínicas Tucumán

San Miguel de Tucumán, Tucumán Province, Argentina

CEMEDIC

Buenos Aires, Argentina

Glenny Corp

Buenos Aires, Argentina

CIPREC

Buenos Aires, Argentina

Asociación de Beneficencia Hospital Sirio Libanés

Buenos Aires, Argentina

Centro Universitario de Investigación en Farmacologia Clínic

Corrientes, Argentina

Instituto de Cardiología "Juana F. Cabral"

Corrientes, Argentina

CIDIM-Centro Integral de Diagnostico por Imagenes Marchegiani

Córdoba, Argentina

Centro Diabetológico Dr. Waitman

Córdoba, Argentina

Instituto Médico Alas

Salta, Argentina

Sanatorio Norte

Santiago del Estero, Argentina

The Effect of Tirzepatide Versus Dulaglutide on Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes (SURPASS-CVOT)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Tirzepatide

Dulaglutide

Ubicaciones

Instituto de Investigaciones Clínicas Bahia Blanca

Organizacion Medica de Investigacion

CEDIC

Stat Research S.A.

Centro de Investigaciones Metabólicas (CINME)

Instituto de Investigaciones Clínicas Mar del Plata

DIM Clínica Privada

Go Centro Medico San Nicolás

Instituto de Investigaciones Clinicas Zarate

Centro Médico Viamonte

Mautalen Salud e Investigación

Centro Medico Dra. Laura Maffei- Investigacion Clinica Aplicada

CEMEDIAB

Centro Medico Privado CEMAIC

Centro Medico Privado San Vicente Diabetes

Instituto Médico Catamarca IMEC

Instituto Médico Fundación Grupo Colaborativo Rosario Investigación y Prevención Medica

Instituto de Investigaciones Clinicas Rosario

Centro de Investigaciones Médicas Tucuman

Clínica Mayo de Urgencias Médicas Cruz Blanca S.R.L

Investigaciones Clínicas Tucumán

CEMEDIC

Glenny Corp

CIPREC

Asociación de Beneficencia Hospital Sirio Libanés

Centro Universitario de Investigación en Farmacologia Clínic

Instituto de Cardiología "Juana F. Cabral"

CIDIM-Centro Integral de Diagnostico por Imagenes Marchegiani

Centro Diabetológico Dr. Waitman

Instituto Médico Alas

Sanatorio Norte

Patrocinadores