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

NCT00234832 | Completed Phase 3 Results DMC

• 1 other identifier: M01-392
• Study Type: interventional
• Target: 10,777
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity

Keywords

Obesity; Sibutramine

Outcome Measures

Primary Outcomes (1)

• Risk of Experiencing a Primary Outcome Event (POE) (i.e., Nonfatal Myocardial Infarction [MI], Nonfatal Stroke, Resuscitated Cardiac Arrest, Cardiovascular [CV] Death)

  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.

  From randomization up to 6 years

Secondary Outcomes (6)

• Risk of Death From Any Cause (All-cause Mortality)

  From randomization up to 6 years

• Risk of Experiencing a POE or a Revascularization Procedure

  From randomization up to 6 years

• Risk of Experiencing a Nonfatal MI Included in the POE

  From randomization up to 6 years

• Risk of Experiencing a Nonfatal Stroke Included in the POE

  From randomization up to 6 years

• Risk of Experiencing a Resuscitated Cardiac Arrest Included in the POE

  From randomization up to 6 years

Study Arms (3)

Sibutramine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Subjects were randomized to receive placebo QD during the Treatment Period after a 6-week Lead-in Period

Drug: Placebo

Lead-in sibutramine

EXPERIMENTAL

All subjects received 10 mg sibutramine QD during a 6-week Lead-in Period

Drug: Sibutramine hydrochloride

Interventions

Sibutramine hydrochloride DRUG

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.)

Also known as: ABT-991, sibutramine, Meridia, Reductil

Sibutramine

Placebo DRUG

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.)

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Abbott: lead

Study Sites (1)

Global Medical Services

North Chicago, Illinois, 60064, United States

Location

Related Publications (5)

• 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.

  PMID: 24534073 DERIVED

• 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.

  PMID: 24406481 DERIVED

• 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.

  PMID: 20818901 DERIVED

• 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.

  PMID: 20184783 DERIVED

• 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.

  PMID: 19828038 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

sibutramine

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Most subjects not indicated for sibutramine (sbt) due to CV disease. Long-term sbt use (6 yrs) regardless of weight loss, is inconsistent with label (limits use to 1-2 yrs \& 5% weight loss). Trial lacked true placebo; all received Lead-in Period sbt.

Results Point of Contact

• Title: Global Medical Services
• Organization: Abbott

800-633-9110

Study Officials

• Cheryl Renz, MD

  Abbott

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: October 10, 2005
• Study Start: January 1, 2003
• Primary Completion: March 1, 2009
• Study Completion: November 1, 2009
• Last Updated: May 11, 2010
• Results First Posted: April 15, 2010

Record last verified: 2010-05

Locations

US (1)