GAstric Bypass to Treat obEse Patients With steAdy hYpertension (GATEWAY)

Phase 3 Randomized Controlled Trial Evaluating the Effect of Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) on Hypertension Medication Reduction, Blood Pressure Levels and Others Cardiovascular Risk Factors.

Phase 3, unicentric, randomized clinical trial, with allocation concealment and intention-to-treat analysis to evaluate the efficacy of videolaparoscopic Roux-en-Y Gastroplasty to decrease the prescription of antihypertensive drugs maintaining normal levels of blood pressure, decrease systemic arterial blood pressure and other risk factors for cardiovascular events compared to clinical treatments of patients with arterial hypertension.

Study Overview

• Status: Completed
• Conditions: Obesity; Systemic Hypertension
• Intervention / Treatment: Procedure: Laparoscopic Roux-en-Y gastric bypass (LRYGB); Other: Clinical treatment

Detailed Description

Randomization:

The randomization list is electronically generated through specific software. A block randomization is conducted with varying block sizes at the rate of 1:1. Confidentiality of the randomization list is ensured by the central automated randomization system, through the Internet, available 24 hours a day (ACT Clinic - Sistema de Estudos Clínicos do IEP HCor).

Blinding Scheme:

Because the study involves a surgical procedure, investigators and patients cannot be blind for treatment allocated to patients.

Roux-en-Y Gastroplasty Patients allocated to surgical treatment will be admitted to the hospital to be subjected to a Roux-en-Y gastric bypass with a biliopancreatic loop of 100cm and a alimentary limb of 150cm.

Antihypertensive Treatment:

The treatment of hypertension will be standardized for all study patients. Prescribed drugs will include preferably a renin-angiotensin blocking system drug and a calcium channels blocker, except if these are contraindicated or the patient has achieved good blood pressure control using other drugs prior to study recruitment. Other drugs can be added at discretion of the attending investigator to achieve a target blood pressure of 130 x 80 mmHg. Patients are treated individually for the other associated comorbidities. Obesity treatment in the control group includes dietary advice, motivation for the practice of physical activities, and drug treatments for diabetes and dyslipidemias if applicable.

Laboratory tests and other exams:

All patients will be subjected to the following measurements throughout the study:

• Outpatient Blood Pressure Monitoring (ABPM)
• Blood pressure measurements taken in doctors' offices:
• Central pressure and associated measurements (SphygmoCor®)
• Polysomnography
• Anthropometry
• Nutritional survey
• Laboratory tests
• Echocardiogram
• Electrocardiogram
• Abdominal ultrasound
• Upper gastrointestinal endoscopy with H.pylori testing

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 04005-000
    • Hospital do Coração - Research Institute
  • SP
    • São Paulo, SP, Brazil, 04004-060
      • Instituto Dante Pazzanese de Cardiologia
    • São Paulo, SP, Brazil, 04004-060
      • Instituto do Coração - Hospital das Clínicas de São Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged between 18 and 65 years old.
• hypertension diagnosis defined as in use of at least 2 high blood pressure medication at full doses.
• body mass index between 30,0 and 39,9 kg/m2.

Exclusion Criteria:

• hypertension ≥ 180/120 mmHg;
• cerebrovascular diseases in the last 6 months.
• Cardiovascular diseases (myocardial infarction, angina, cardiac failure) in the last 6 months.
• Baseline psychiatric disorders: schizophrenia, bipolar disorder, severe depression, psychosis.
• Renal diseases: diabetic nephropathy, creatinine clearance < 30 ml/min.
• Patients with secondary hypertension except due to the sleep apnea.
• Advanced peripheral arterial disease
• atrophic gastritis
• Diabetes mellitus type 1 and type 2 with HbA1 c >7,0%
• alcoholism or use of illicit drugs
• smokers
• previous laparotomy
• severe hepatic disorders
• Pregnancy or women not using effective contraceptive methods.
• Recent neoplasm (< 5 years)
• Immunosuppressant drugs
• Unable to understanding and follow the study protocol orientations.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Laparoscopic Roux-en-Y gastric bypass; Laparoscopic Roux-en-Y gastric bypass performed as a treatment for obesity.	Procedure: Laparoscopic Roux-en-Y gastric bypass (LRYGB); Laparoscopic Roux-en-Y gastric bypass (LRYGB)is the one of the techniques of bariatric surgery; Other: Clinical treatment; Medical treatment aiming the control of risk factors for cardiovascular diseases (including adequate control of blood pressure), psychological assistance and dietetic advice for body weight reduction.
Active Comparator: Clinical treatment; Optimized clinical treatment including medical management of hypertension.	Other: Clinical treatment; Medical treatment aiming the control of risk factors for cardiovascular diseases (including adequate control of blood pressure), psychological assistance and dietetic advice for body weight reduction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Reduction in the Number of Anti-hypertensive Drugs Used and Maintaining Blood Pressure Below 140x90mmHg	Evaluate the efficacy of Roux-en-Y Gastric Bypass on the reduction of the number of antihypertensive drugs, maintaining a controlled blood pressure (<140x90 mmHg), in 12 months.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of Roux-en-Y Gastroplasty to Decrease the Number of Antihypertensive Drugs.	Evaluate the efficacy of Roux-en-Y Gastric Bypass on the reduction of the number of antihypertensive drugs, maintaining a controlled blood pressure (<140x90 mmHg).	12, 24, 36, 48 and 60 months
Absolute Change From Baseline in Blood Pressure Levels	Change on systemic blood pressure assessed by ambulatory blood pressure monitoring (ABPM).	12, 24, 36, 48 and 60 months
Effect on Central Blood Pressure Augmentation Index and Pulse Wave Velocity	Change on central blood pressure augmentation index and pulse wave velocity as measured by SphygmoCor device	12, 24, 36, 48 and 60 months
Absolute Change From Baseline on Systolic Blood Pressure	Absolute change from baseline in systolic blood pressure	12, 24, 36, 48 and 60 months
Absolute Change From Baseline on Diastolic Blood Pressure	Absolute change from baseline in diastolic blood pressure	12, 24, 36, 48 and 60 months
Absolute Change From Baseline on Weight Loss	Absolute change from baseline on weight loss	12, 24, 36, 48 and 60 months
Absolute Change From Baseline on BMI	Absolute change from baseline on BMI	12, 24, 36, 48 and 60 months
Absolute Change From Baseline on Waist Circumference	Absolute change from baseline on waist circumference	12, 24, 36, 48 and 60 months
Absolute Change From Baseline on Fasting Plasm Glucose Level, HbA1c and Insulin Resistance	Change from baseline on fasting plasm glucose level, HbA1c and insulin resistance	12, 24, 36, 48 and 60 months
Absolute Change From Baseline on LDL-cholesterol Level	Absolute change from baseline on LDL-cholesterol level	12, 24, 36, 48 and 60 months
Absolute Change From Baseline on HDL-cholesterol Level	Absolute change from baseline on HDL-cholesterol level	12, 24, 36, 48 and 60 months
Absolute Change From Baseline on Triglycerides Levels	Absolute change from baseline on triglycerides levels	12, 24, 36, 48 and 60 months
Absolute Change From Baseline on Uric Acid Levels	Absolute change from baseline on uric acid levels	12, 24, 36, 48 and 60 months
Absolute Change From Baseline on Ultra-sensitive CRP Levels	Absolute change from baseline on ultra-sensitive CRP levels	12, 24, 36, 48 and 60 months
Absolute Change From Baseline of Cardiovascular Risk	Absolute change from baseline of cardiovascular risk calculated by Framingham Score	12, 24, 36, 48 and 60 months
Change on Heart Anatomy	Change on heart anatomy as evaluated by echocardiogram	12, 24, 36, 48 and 60 months
Change on Sleep Quality	Change on sleep quality as evaluated by polysomnography	12, 24, 36, 48 and 60 months
Adverse Events	Describe the main adverse events	At any time during the study period

Collaborators and Investigators

• Sponsor: Hospital do Coracao
• Collaborators: Ethicon Endo-Surgery
• Investigators: Principal Investigator: Carlos A Schiavon, MD, PhD, Hospital do Coracao

Publications and helpful links

General Publications

• Schiavon CA, Bersch-Ferreira AC, Santucci EV, Oliveira JD, Torreglosa CR, Bueno PT, Frayha JC, Santos RN, Damiani LP, Noujaim PM, Halpern H, Monteiro FLJ, Cohen RV, Uchoa CH, de Souza MG, Amodeo C, Bortolotto L, Ikeoka D, Drager LF, Cavalcanti AB, Berwanger O. Effects of Bariatric Surgery in Obese Patients With Hypertension: The GATEWAY Randomized Trial (Gastric Bypass to Treat Obese Patients With Steady Hypertension). Circulation. 2018 Mar 13;137(11):1132-1142. doi: 10.1161/CIRCULATIONAHA.117.032130. Epub 2017 Nov 13. Erratum In: Circulation. 2019 Oct;140(14):e718.
• Schiavon CA, Ikeoka D, Santucci EV, Santos RN, Damiani LP, Bueno PT, Oliveira JD, Torreglosa CR, Bersch-Ferreira AC, Miranda TA, Barros S, Halpern H, Monteiro FLJ, Cohen RV, Noujaim PM, de Souza MG, Amodeo C, Bortolotto LA, Berwanger O, Cavalcanti AB, Drager LF. Effects of Bariatric Surgery Versus Medical Therapy on the 24-Hour Ambulatory Blood Pressure and the Prevalence of Resistant Hypertension. Hypertension. 2019 Mar;73(3):571-577. doi: 10.1161/HYPERTENSIONAHA.118.12290.
• Schiavon CA, Santos RN, Santucci EV, Noujaim PM, Cavalcanti AB, Drager LF. Does the RYGB common limb length influence hypertension remission and cardiometabolic risk factors? Data from the GATEWAY trial. Surg Obes Relat Dis. 2019 Feb;15(2):211-217. doi: 10.1016/j.soard.2018.11.022. Epub 2018 Nov 27.
• Schiavon CA, Bhatt DL, Ikeoka D, Santucci EV, Santos RN, Damiani LP, Oliveira JD, Machado RHV, Halpern H, Monteiro FLJ, Noujaim PM, Cohen RV, de Souza MG, Amodeo C, Bortolotto LA, Berwanger O, Cavalcanti AB, Drager LF. Three-Year Outcomes of Bariatric Surgery in Patients With Obesity and Hypertension : A Randomized Clinical Trial. Ann Intern Med. 2020 Nov 3;173(9):685-693. doi: 10.7326/M19-3781. Epub 2020 Aug 18.
• Schiavon CA, Ikeoka DT, de Sousa MG, Silva CR, Bersch-Ferreira AC, de Oliveira JD, Noujaim PM, Cohen RV, Amodeo C, Berwanger O; GATEWAY (GAstric bypass surgery to TrEat patients With steAdy hYpertension) Investigators. Effects of gastric bypass surgery in patients with hypertension: rationale and design for a randomised controlled trial (GATEWAY study). BMJ Open. 2014 Sep 8;4(9):e005702. doi: 10.1136/bmjopen-2014-005702.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2013
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): February 1, 2022

Study Registration Dates

• First Submitted: February 4, 2013
• First Submitted That Met QC Criteria: February 5, 2013
• First Posted (Estimate): February 6, 2013

Study Record Updates

• Last Update Posted (Actual): April 7, 2022
• Last Update Submitted That Met QC Criteria: March 25, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: obesity; hypertension; bariatric surgery; high blood pressure; Laparoscopic Roux-en-Y gastric bypass (LRYGB)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: IEP2013_HAS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED