Primary objective:To assess the effect of treatment with liraglutide compared to placebo for at least 3.5 yearand up to 5 years on the incidence of cardiovascular events, as defined by the belowprimary and secondary endpoints, in adults with type 2…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Endpoint:
The primary objective will be addressed using the following primary endpoint:
Time from randomisation to first occurrence of cardiovascular death, non-fatal
myocardial
infarction, or non-fatal stroke (a composite cardiovascular outcome)
Secondary outcome
The following secondary endpoints will be used as supportive endpoints for the
primary objective:
• Time from randomisation to first occurrence of an expanded composite
cardiovascular
outcome, defined as either cardiovascular death, non-fatal myocardial
infarction, non-fatal
stroke, revascularisation, unstable angina or hospitalisation for chronic heart
failure
• Time from randomisation to all cause death
• Time from randomisation to each individual component of the expanded composite
cardiovascular outcome
The following secondary endpoints will be used as supportive endpoints for the
secondary
objective:
• Time from randomisation to first occurrence of a composite microvascular
outcome, defined
as either a need for retinal photocoagulation or vitreous haemorrhage or
diabetes-related
blindness or new or worsening nephropathy (defined as new onset of
macroalbuminuria, or
doubling of serum creatinine level and creatinine clearance per modification of
diet in renal
disease (MDRD) <= 45 mL/min/1.73m2, or the need for continuous renal-replacement
therapy
(in the absence of an acute reversible cause), or death due to renal disease)
• Time from randomisation to each individual component of the composite
microvascular
outcome
• Diabetic foot ulcer
• Change from baseline to the last assessment during the treatment period in:
* Weight and waist circumference
* HbA1c
* Blood lipids: total cholesterol, HDL-cholesterol, LDL-cholesterol and
triglycerides
* Blood pressure and pulse rate
* Selected aboratory parameters:
• Incidence of hypoglycaemic episodes
• Incidence of serious adverse events (SAE) and the following medical events of
special interest
(MESI): Neoplasm, Pancreatitis or acute, severe and persistent abdominal pain
leading to a
suspicion of pancreatitis, Acute gallstone disease (biliary colic or acute
cholecystitis), First
confirmed episode of calcitonin concentration increase >= 20 ng/L, Thyroid
disease, Severe
hypoglycaemic event, Immunogenicity event (antibody formation, allergic
reactions, immunecomplex
disease and injection site disorders), Adverse events leading to treatment
discontinuation (if not any of the mentioned MESIs)
Background summary
The primary purpose of this trial is to determine the long-term effect of
liraglutide on
cardiovascular outcomes and other clinically important events.
The number of patients exposed to treatment and treatment duration will be
substantially
larger compared to the already completed phase 3 programme, which will enable
the
evaluation of liraglutide*s effects on clinically important outcomes:
cardiovascular,
microvascular and additional safety outcomes selected based on the information
derived
from the pre-registration programme.
The trial has been designed in order to accommodate the requirements contained
in the
FDA guidance document *Evaluating Cardiovascular Risk in New Anti-diabetic
Therapies
to Treat Type 2 Diabetes*
The trial will also determine the long-term effects of liraglutide on treatment
surrogates,
namely glycaemic control, weight, waist circumference, lipid profile and blood
pressure.
Study objective
Primary objective:
To assess the effect of treatment with liraglutide compared to placebo for at
least 3.5 year
and up to 5 years on the incidence of cardiovascular events, as defined by the
below
primary and secondary endpoints, in adults with type 2 diabetes that are at
high risk for
cardiovascular events
Secondary objectives:
To assess the efficacy and safety with regard to clinically important events or
other
surrogate parameters of treatment with liraglutide compared to placebo in
adults with type
2 diabetes that are at high risk for cardiovascular events
Study design
The trial consist of a screening visit followed by a open label run-in period
of two weeks. After the run-in period patients will be randomised to either
treatment with liraglutide once daily injections or once daily placebo
injections. The dosing of liraglutide or placebo will be increased per week
(during a period of 3 weeks) from 0,6mg, 1,2mg up to a maximum 1,8mg. The
treatment of liraglutide or placebo is in addition to the standard of care.
Intervention
Once daily injections with either liraglutide or once daily injections with
placebo.
Study burden and risks
It's possible that bloodwithdrawals or self measurements of blood glucose
values can cause haemorrhages or discomfort. If instructions of the pen
injector are not followed or misused it's possible that patients administer the
wrong dose of liraglutide or placebo. despite the fact that liraglutide's mode
of action is glucose dependent there is a minor chance of experiencing low
blood glucose values (hypo's). Local allergic reactions are possible or pain at
the injection side is possible. The patient could experience side effects from
liraglutide
Flemingweg 18
2408 AV Alphen a/d Rijn
NL
Flemingweg 18
2408 AV Alphen a/d Rijn
NL
Listed location countries
Age
Inclusion criteria
• Men or women with type 2 diabetes
• Age >= 50 years at screening and concomitant cardiovascular, cerebrovascular or peripheral
vascular disease or chronic renal failure or chronic heart failure OR age >= 60 years at
screening and other specified risk factors of vascular disease
• HbA1c >= 7.0% at screening
Exclusion criteria
1.Type 1 diabetes
2. Use of a GLP-1 receptor agonist (exenatide, liraglutide or other) or pramlintide or any
(dipeptidyl peptidase 4 (DPP-4) inhibitor within the 3 months prior to screening
3.Use of insulin other than human neutral protamine hagedorn (NPH) insulin or long-acting
insulin analogue within 3 months prior to screening. Short-term use of other insulin during this
period in connection with intercurrent illness is allowed at Investigator*s discretion
4.Acute decompensation of glycaemic control requiring immediate intensification of treatment to
prevent acute complications of diabetes (e.g., diabetic ketoacidosis) in the previous 3 months
5.An acute coronary or cerebrovascular event in the previous 14 days
6. Current continuous renal replacement therapy
7.End-stage liver disease
8.Chronic heart failure NYHA IV
9.A prior solid organ transplant or awaiting solid organ transplant
10.Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial
medullary thyroid carcinoma (FMTC)
11.Personal history of non-familial medullary thyroid carcinoma
12. Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy in the
previous 5 years. Subjects with intraepithelial squamous cell carcinoma of the skin (Bowen*s
disease) treated with topical 5-fluorouracil (5FU) and subjects with basal cell skin cancer are
allowed to enter the trial
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-012201-19-NL |
| CCMO | NL32383.091.10 |