Clinical trial NCT00234832: A Long Term Study of Sibutramine and the Role of Obesity Management in Relation to Cardiovascular Disease in Overweight and Obese Patients
Official title: Sibutramine Cardiovascular Morbidity/Mortality Outcomes Study in Overweight or Obese Subjects at Risk of a Cardiovascular Event
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Obesity
Keywords: Obesity
Sibutramine
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2005-10-10
Enrollment: 10777
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study was to determine the long-term effect of sibutramine treatment on cardiovascular outcomes in overweight and obese patients at risk of a cardiovascular event.

Detailed description: The study consisted of 4 periods: 1) a Screening Period of approximately 2 weeks; 2) a 6-week Lead-in Period, during which subjects received single-blind sibutramine and country-specific standard of care for weight management. Subjects who discontinued study drug treatment during the Lead-in Period were not randomized and did not participate in the double-blind Treatment Period or the Follow-up Period; 3) a double-blind Treatment Period in which subjects were randomized to 1 of the 2 treatment groups and were followed until the study ended; and 4) a double-blind Follow-up Period, during which randomized subjects who discontinued study drug were followed until the study ended. The Randomization Phase consisted of the double-blind Treatment Period and the double-blind Follow-up Period. Subjects received country-specific standard of care for weight management during the Randomization Phase.

An independent events adjudication committee evaluated all potential cardiovascular outcome events and confirmed the outcome events and time of onset to be included in the statistical analyses.

Eligibility criteria: Inclusion Criteria:

* Subject's body mass index (BMI) was \>= 27 kg/m(2) and \<= 45 kg/m(2) or their BMI was \>= 25 kg/m(2) and \< 27 kg/m(2) with waist circumference of \>= 102 cm in males or \>= 88 cm in females.
* Medical history positive for:

  * Preexisting cardiovascular disease (i.e., coronary artery disease, cerebrovascular disease, or peripheral arterial occlusive disease) and/or
  * Type 2 diabetes mellitus with at least 1 other risk factor (i.e., dyslipidemia, controlled hypertension, current smoker, or diabetic nephropathy with evidence of microalbuminuria)

Exclusion Criteria:

* History of recent myocardial infarction.
* Heart failure symptoms greater than New York Heart Association Functional Class II.
* Hemodynamically significant valvular or left ventricular (LV) tract obstruction.
* Subjects without a pacemaker and with any of the following:

  * Sinus bradycardia (\< 50 bpm)
  * Sick sinus syndrome
  * Atrioventricular block of more than 1st degree
* Mean sitting systolic blood pressure (SBP) \> 160 mmHg. Mean sitting diastolic blood pressure (DBP) \> 100 mmHg. Mean sitting heart rate (HR) \> 100 bpm.
* Syncopal episodes presumed to be due to uncontrolled life-threatening arrhythmias.
* Planned cardiac surgery or coronary angioplasty within 6 months of screening.
* History of recent non-hemorrhagic stroke or transient ischemic attack (TIA), history of hemorrhagic stroke.
* Hyperthyroidism.
* Known chronic liver disease or endstage renal disease.
* Severe, symptomatic benign prostatic hyperplasia which may require surgery.
* Known pheochromocytoma, history of narrow angle glaucoma, Gilles de la Tourette syndrome, history of seizures, history of bariatric or abdominal obesity surgery (excluding liposuction).
* Concomitant use of monoamine oxidase inhibitors or drugs that increase levels of serotonin in the brain.
* Treated hypertension stabilized for less than 3 months.
* Inability to perform regular physical activity.

Primary outcomes:
measure: Risk of Experiencing a Primary Outcome Event (POE) (i.e., Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, Resuscitated Cardiac Arrest, Cardiovascular [CV] Death)
timeFrame: From randomization up to 6 years
Secondary outcomes:
measure: Risk of Death From Any Cause (All-cause Mortality)
timeFrame: From randomization up to 6 years
measure: Risk of Experiencing a POE or a Revascularization Procedure
timeFrame: From randomization up to 6 years
measure: Risk of Experiencing a Nonfatal MI Included in the POE
timeFrame: From randomization up to 6 years
measure: Risk of Experiencing a Nonfatal Stroke Included in the POE
timeFrame: From randomization up to 6 years
measure: Risk of Experiencing a Resuscitated Cardiac Arrest Included in the POE
timeFrame: From randomization up to 6 years
measure: Risk of Experiencing Cardiovascular Death Included in the POE
timeFrame: From randomization up to 6 years
Other outcomes:
Locations:
city: North Chicago
country: United States
facility: Global Medical Services
state: Illinois
Study officials:
affiliation: Abbott
name: Cheryl Renz, MD
role: STUDY_DIRECTOR
References:
citation: Jorgensen ME, Torp-Pedersen C, Finer N, Caterson I, James WP, Legler UF, Andersson C. Association between serum bilirubin and cardiovascular disease in an overweight high risk population from the SCOUT trial. Nutr Metab Cardiovasc Dis. 2014 Jun;24(6):656-62. doi: 10.1016/j.numecd.2013.12.009. Epub 2014 Jan 18.
citation: Seimon RV, Espinoza D, Ivers L, Gebski V, Finer N, Legler UF, Sharma AM, James WP, Coutinho W, Caterson ID. Changes in body weight and blood pressure: paradoxical outcome events in overweight and obese subjects with cardiovascular disease. Int J Obes (Lond). 2014 Sep;38(9):1165-71. doi: 10.1038/ijo.2014.2. Epub 2014 Jan 10.
citation: James WP, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, Torp-Pedersen C, Sharma AM, Shepherd GM, Rode RA, Renz CL; SCOUT Investigators. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med. 2010 Sep 2;363(10):905-17. doi: 10.1056/NEJMoa1003114.
citation: Weeke P, Andersson C, Fosbol EL, Brendorp B, Kober L, Sharma AM, Finer N, James PT, Caterson ID, Rode RA, Torp-Pedersen C. The weight lowering effect of sibutramine and its impact on serum lipids in cardiovascular high risk patients with and without type 2 diabetes mellitus - an analysis from the SCOUT lead-in period. BMC Endocr Disord. 2010 Feb 26;10:3. doi: 10.1186/1472-6823-10-3.
citation: Andersson C, Weeke P, Brendorp B, Kober L, Fosbol EL, Sharma AM, Finer N, Caterson ID, Rode RA, James PT, Torp-Pedersen C. Differential changes in serum uric acid concentrations in sibutramine promoted weight loss in diabetes: results from four weeks of the lead-in period of the SCOUT trial. Nutr Metab (Lond). 2009 Oct 14;6:42. doi: 10.1186/1743-7075-6-42.