The ORIGIN Trial (Outcome Reduction With Initial Glargine Intervention) (ORIGIN)

This study has been completed.

Sponsor:

Collaborator:

Population Health Research Institute

Information provided by (Responsible Party):

Sanofi

ClinicalTrials.gov Identifier:

NCT00069784

First received: October 1, 2003

Last updated: January 24, 2013

Last verified: January 2013

History of Changes

Results First Received: December 18, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Diabetes Mellitus, Non-Insulin-Dependent
Interventions:	Drug: insulin glargine (HOE901) Drug: omega-3 polyunsaturated fatty acids (PUFA) Drug: placebo Device: reusable pen device for insulin injection

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted at 575 sites in 40 countries between August 22, 2003 and December 19, 2011. Three sites were closed and data from these sites were not analyzed following site audits and in compliance with rulings from national health authorities.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The purpose of the factorial design was to efficiently answer two independent scientifically worthwhile questions regarding insulin glargine and omega-3 fatty acids within the context of a single clinical trial. Sample size was determined based on the insulin glargine study objective. Results reported below are those of the insulin glargine study.

Reporting Groups

	Description
Insulin Glargine	Treatment with Insulin Glargine with or without omega-3 polyunsaturated fatty acids
Standard Care	Standard care with or without omega-3 polyunsaturated fatty acids

Participant Flow: Overall Study

	Insulin Glargine	Standard Care
STARTED	6264 ^[1]	6273 ^[1]
Safety Population (Treated)	6231 ^[2]	6273 ^[3]
COMPLETED	5052 ^[4]	6273 ^[5]
NOT COMPLETED	1212	0
Adverse Event	105	0
Withdrawal by Subject	1090	0
Other	17	0

^[1]	randomized participants = intent-to-treat (ITT) population
^[2]	randomized patients who received at least one dose of insulin glargine
^[3]	patients randomized to standard care arm
^[4]	completed study treatment
^[5]	not applicable (no treatment)

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups

	Description
Insulin Glargine	Treatment with Insulin Glargine with or without omega-3 polyunsaturated fatty acids
Standard Care	Standard care with or without omega-3 polyunsaturated fatty acids
Total	Total of all reporting groups

Baseline Measures

Insulin Glargine

Standard Care

Total

Overall Participants Analyzed
[Units: Participants]

6264

6273

12537

Age
[Units: Years]
Mean (Standard Deviation)

63.5 (7.8)

63.5 (7.9)

63.5 (7.8)

Gender, Customized
[Units: Participants]

Male

4181

3969

8150

Female

2082

2304

4386

Missing value

Baseline Weight ^[1]
[Units: Kg]
Mean (Standard Deviation)

83.33 (16.77)

83.13 (17.28)

83.23 (17.03)

^[1]	Due to missing values, N=6256 for insulin glargine and N=6271 for standard care.

Baseline Body Mass Index ^[1]
[Units: Kg/m²]
Mean (Standard Deviation)

29.77 (5.17)

29.88 (5.33)

29.82 (5.25)

^[1]	Due to missing values, N=6251 for insulin glargine and N=6270 for standard care.

Any previous cardiovascular event
[Units: Participants]

2552

2607

5159

Yes

3712

3666

7378

Diabetes diagnosis at time of screening ^[1]
[Units: Participants]

IFG and/or IGT

735

717

1452

Newly diagnosed diabetic

365

395

760

Established diabetes with no OAD treatment

1414

1467

2881

Established diabetes with one OAD treatment

3748

3692

7440

Unclear diabetes status

^[1]

IFG = Impaired Fasting Glucose defined as a Postprandial Plasma Glucose (PPG) value ≥140 and <200 mg/dL (ie, ≥7.8 and <11.1 mmol/L), with a Fasting Plasma Glucose (FPG) <126 mg/dL (7.0 mmol/L)

IGT = Impaired Glucose Tolerance defined as an FPG ≥110 and <126 mg/dL (≥6.1 and <7 mmol/L), without diabetes mellitus (PPG must be <200 mg/dL [11.1 mmol/L])

OAD = oral antidiabetic drug

Duration of diabetes for established diabetes patients ^[1]
[Units: Years]
Median (Inter-Quartile Range)

3.50
(1.50 to 7.50)

^[1]	Population of patients with established diabetes. Due to missing values, N=5148 for insulin glargine and N=5141 for standard care.

Glycated Hemoglobin A1c (HbA1c) ^[1]
[Units: Percent]
Median (Inter-Quartile Range)

6.41
(5.81 to 7.18)

6.40
(5.81 to 7.16)

6.40
(5.81 to 7.18)

^[1]	Due to missing values, N=6175 for insulin glargine and N=6189 for standard care.

Fasting Plasma Glucose ^[1]
[Units: mmol/L]
Median (Inter-Quartile Range)

6.94
(6.05 to 8.20)

6.90
(6.00 to 8.20)

6.94
(6.05 to 8.20)

^[1]	Due to missing values, N=6248 for insulin glargine and N=6266 for standard care.

Outcome Measures

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1. Primary:

Composite of the First Occurrence of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI) or Nonfatal Stroke [ Time Frame: from randomization until study cut-off date (median duration of follow-up: 6.2 years) ]

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2. Primary:

Composite of the First Occurrence of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, Revascularization Procedure or Hospitalization for Heart Failure (HF) [ Time Frame: from randomization until study cut-off date (median duration of follow-up: 6.2 years) ]

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3. Secondary:

Total Mortality (All Causes) [ Time Frame: from randomization until study cut-off date (median duration of follow-up: 6.2 years) ]

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4. Secondary:

Composite Diabetic Microvascular Outcome (Kidney or Eye Disease) [ Time Frame: from randomization until study cut-off date (median duration of follow-up: 6.2 years) ]

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5. Secondary:

Incidence of Development of Type 2 Diabetes Mellitus in Participants With IGT and/or IFG [ Time Frame: from randomization until the last follow-up visit or last OGTT (median duration of follow-up: 6.2 years) ]

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6. Other Pre-specified:

Number of Patients With Various Types of Symptomatic Hypoglycemia Events [ Time Frame: on-treatment period (median duration of follow-up: 6.2 years) ]

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7. Other Pre-specified:

Number of Patients With First Occurrence of Any Type of Cancer [ Time Frame: from randomization until study cut-off date (median duration of follow-up: 6.2 years) ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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