A Long Term Study of Sibutramine and the Role of Obesity Management in Relation to Cardiovascular Disease in Overweight and Obese Patients - Full Text View

Sponsor:	Abbott
Information provided by:	Abbott
ClinicalTrials.gov Identifier:	NCT00234832

Purpose

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.

Condition	Intervention	Phase
Obesity	Drug: Sibutramine hydrochloride Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Sibutramine Cardiovascular Morbidity/Mortality Outcomes Study in Overweight or Obese Subjects at Risk of a Cardiovascular Event

Resource links provided by NLM:

MedlinePlus related topics: Obesity

Drug Information available for: Sibutramine Sibutramine hydrochloride monohydrate

U.S. FDA Resources

Further study details as provided by Abbott:

Primary Outcome Measures:

Risk of Experiencing a Primary Outcome Event (POE) (i.e., Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, Resuscitated Cardiac Arrest, Cardiovascular [CV] Death) [ Time Frame: From randomization up to 6 years ] [ Designated as safety issue: Yes ]
For each subject, POE status (with/without an event) and time to first occurrence of a POE using time-to-event analysis were evaluated. All POE confirmed by an independent adjudication committee were included in the analysis.

Secondary Outcome Measures:

Risk of Death From Any Cause (All-cause Mortality) [ Time Frame: From randomization up to 6 years ] [ Designated as safety issue: Yes ]
For each subject who died, the time to death was evaluated using time-to-event analysis.
Risk of Experiencing a POE or a Revascularization Procedure [ Time Frame: From randomization up to 6 years ] [ Designated as safety issue: Yes ]
This outcome includes nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, CV death (including events such as fatal MI and fatal stroke), and any of the following revascularization procedures: percutaneous transluminal coronary angioplasty, coronary artery bypass graft, coronary artery stent placement, cardiac transplant, peripheral vascular bypass or angioplasty, and carotid endarterectomy. For each subject, the POE or revascularization status (yes/no) and time to first occurrence of an event using time-to-event analysis were evaluated.
Risk of Experiencing a Nonfatal MI Included in the POE [ Time Frame: From randomization up to 6 years ] [ Designated as safety issue: Yes ]
For each subject, the first occurrence of a nonfatal MI included in the POE was evaluated using time-to-event analysis.
Risk of Experiencing a Nonfatal Stroke Included in the POE [ Time Frame: From randomization up to 6 years ] [ Designated as safety issue: Yes ]
For each subject, the time to first occurrence of a nonfatal stroke included in the POE was evaluated using time-to-event analysis.
Risk of Experiencing a Resuscitated Cardiac Arrest Included in the POE [ Time Frame: From randomization up to 6 years ] [ Designated as safety issue: Yes ]
For each subject, the time to first occurrence of a resuscitated cardiac arrest included in the POE was evaluated using time-to-event analysis.
Risk of Experiencing Cardiovascular Death Included in the POE [ Time Frame: From randomization up to 6 years ] [ Designated as safety issue: Yes ]
For each subject, the time to cardiovascular death included in the POE was evaluated using time-to-event analysis.

Enrollment:	10777
Study Start Date:	January 2003
Study Completion Date:	November 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sibutramine Subjects were randomized to receive sibutramine 10 mg once daily (QD) during the Treatment Period after a 6-week Lead-in Period	Drug: Sibutramine hydrochloride One 10 mg tablet QD plus country-specific standard care for weight management. (During the Treatment Period, the dose could have been titrated up to 15 mg at the investigator's discretion.) Other Names: ABT-991 sibutramine Meridia Reductil
Placebo Comparator: Placebo Subjects were randomized to receive placebo QD during the Treatment Period after a 6-week Lead-in Period	Drug: Placebo 1 tablet QD plus country-specific standard care for weight management (During the Treatment Period, the dose could have been titrated up to 15 mg at the investigator's discretion.) Other Name: Placebo
Experimental: Lead-in sibutramine All subjects received 10 mg sibutramine QD during a 6-week Lead-in Period	Drug: Sibutramine hydrochloride 10 mg tablet QD during the 6-week Lead-in Period plus country-specific standard care for weight management

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

Ages Eligible for Study:	55 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00234832

Locations

United States, Illinois
Global Medical Services
North Chicago, Illinois, United States, 60064

Sponsors and Collaborators

Abbott

Investigators

Study Director:

Cheryl Renz, MD

Abbott

More Information

Additional Information:

package insert information This link exits the ClinicalTrials.gov site

No publications provided by Abbott

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Cheryl Renz, MD, Abbott
ClinicalTrials.gov Identifier:	NCT00234832 History of Changes
Other Study ID Numbers:	M01-392
Study First Received:	September 13, 2005
Results First Received:	March 26, 2010
Last Updated:	May 6, 2010
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Abbott:

Obesity
Sibutramine

Additional relevant MeSH terms:

Cardiovascular Diseases
Obesity
Overweight
Overnutrition
Nutrition Disorders
Body Weight
Signs and Symptoms
Sibutramine

Appetite Depressants
Anti-Obesity Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antidepressive Agents
Psychotropic Drugs

ClinicalTrials.gov processed this record on February 09, 2012