Perioperative Insulin, GIK or GLP-1 Treatment in Diabetes Mellitus (PILGRIM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor:
Information provided by (Responsible Party):
B Preckel, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT02036372
First received: January 10, 2014
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

The incidence of diabetes mellitus type II is increasing. More and more patients who need surgery have diabetes mellitus type II. Despite an enormous amount of glucose lowering protocols and the proven negative effects of hyperglycaemia. There is no evidence for the optimal glucose lowering protocol.

This study investigates the optimal intraoperative treatment algorithm to lower glucose in patients with diabetes mellitus type 2 undergoing non-cardiac surgery, comparing intraoperative glucose-insulin-potassium infusion (GIK), insulin bolus regimen (BR) and GLP-1 (liraglutide, LG) treatment.


Condition Intervention
Diabetes Mellitus Type II
Drug: Liraglutide
Drug: Insulin bolus
Drug: GIK infusion

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PILGRIM - Perioperative Insulin, GIK or GLP-1 Treatment in Diabetes Mellitus Type II

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • Median glucose [ Time Frame: 1 hour after surgery ] [ Designated as safety issue: No ]
    The difference in median glucose between the GIK, BR and LG group 1 hour after surgery


Secondary Outcome Measures:
  • Total Insulin administration [ Time Frame: 1 day postoperative ] [ Designated as safety issue: No ]
    The difference in insulin administration between the GIK, BR and LG group within 24 h after start of surgery

  • Median glucose [ Time Frame: 4 hours and 1 day postoperative ] [ Designated as safety issue: No ]
    The difference in median glucose between the GIK, BR and LG group 4 hours and 1 day after surgery

  • Postoperative complications [ Time Frame: 1 month after surgery ] [ Designated as safety issue: No ]
    The difference in proportion of any postoperative complication within the first month

  • Hypoglycemia [ Time Frame: From start treatment until the morning of day 1 postoperative ] [ Designated as safety issue: Yes ]
    The occurrence of mild and severe hypoglycemia (glucose <4.0 mmol/l and <2.3 mmol/l, respectively) during and up to 24 h after surgery

  • Hypo- and hyperkalemia [ Time Frame: from start treatment until morning of day 1 postoperative ] [ Designated as safety issue: Yes ]
    The occurrence of hypokalemia (<3.5 mmol/l) and hyperkalemia (>5.0 mmol/l) during and up to 24 h after surgery


Estimated Enrollment: 315
Study Start Date: January 2014
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BR (bolus regimen)
  • Day before surgery: half evening dose long acting insulin
  • Day of surgery:

    • patients using mealtime and longacting insulin/NPH: withhold mealtime morning dose, stop glucose lowering tablets
    • patients using only long acting insulin/NPH: half dose of long-acting or NPH insulin, stop glucose lowering tablets
  • Measure blood glucose every 60 minutes, start 30 min prior to surgery
  • Give bolus of insulin according to treatment algorithm
Drug: Insulin bolus
Other Name: novorapid
Experimental: LG (Liraglutide)
  • Day before surgery: half dose of long acting and mealtime insulin from start liraglutide
  • Day of surgery: withhold own insulin, stop oral glucose lowering tablets
  • Start with 0.6 mg liraglutide subcutaneously (s.c.) the day prior to surgery at 17.00hr.
  • In case of nausea graded higher than minimal, the patient will be excluded from the study
  • Otherwise, treatment will be continued with 1.2 mg liraglutide s.c. per day on the day of surgery at 07.00hr.
  • Measure glucose every 60 minutes, start 30 min prior to surgery
  • Adjust according to bolus algorithm of BR group
Drug: Liraglutide
Other Name: Victoza
Drug: Insulin bolus
Other Name: novorapid
Active Comparator: GIK (glucose -insulin - potassium) infusion
  • Day before surgery: half evening dose long acting insulin
  • Day of surgery: stop oral glucose lowering tablets and withhold own insulin.
  • GIK infusion: 500 cc glucose 5% with insulin and 10 mmol KCL per 500 cc. Start at 83 ml/hr.
  • Calculate the insulin amount in the GIK infusion according to the formula:

I= (PG-7)/(200/W)+8 I=Insulin amount, PG=glucose 30 minutes preoperative, W= body weight in kg

  • Measure blood glucose every 60 minutes, start 30 min prior to surgery
  • Adjust glucose > 8 mmol/l according to treatment algorithm
Drug: GIK infusion
continuous infusion
Other Name: glucose, insulin, potassium infusion

Detailed Description:

Diabetes mellitus is associated with poor outcome after surgery. The prevalence of diabetes in hospitalised patients is up to 40%, meaning that the anaesthesiologist will encounter a diabetes patient in the operating room on a daily basis. Multiple protocols for perioperative glucose regulation have been developed, ranging from intravenous glucose-insulin-potassium infusion to subcutaneous bolus regimens. Despite this abundance of published glucose lowering protocols and the proven negative effects of intraoperative hyperglycaemia in diabetes, there is no evidence regarding the optimal intraoperative glucose lowering treatment. Recently, incretins have been introduced to lower blood glucose. The main hormone of the incretin system is glucagon-like peptide-1 (GLP-1). GLP-1 increases insulin and decreases glucagon secretion in a glucose-dependent manner, resulting in low incidence of hypoglycaemia. This study investigates for the first time the optimal intraoperative treatment algorithm to lower glucose in patients with diabetes mellitus undergoing non-cardiac surgery.

Objective:

This study investigates the optimal intraoperative treatment algorithm to lower glucose in patients with diabetes mellitus type 2 undergoing non-cardiac surgery, comparing intraoperative glucose-insulin-potassium infusion (GIK), insulin bolus regimen (BR) and GLP-1 (liraglutide, LG) treatment.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent
  • known diabetes mellitus type II for > 3 months
  • aged 18-75 years
  • scheduled for elective non-cardiac surgery
  • daily insulin dosage of < 0.5IU/kg body weight

Exclusion Criteria:

  • Oral corticosteroid use
  • Planned for day-care (ambulant) surgery
  • Planned ICU stay post-operatively
  • Planned bowel surgery
  • History of chronic pancreatitis or idiopathic acute pancreatitis
  • Impaired liver function, defined as alanine aminotransferase (ALAT) ≥ 2.5 times upper normal limit
  • Impaired renal function defined as serum-creatinine ≥ 133 μmol/L for males and ≥ 115 μmol/L for females
  • Females of child bearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (adequate contraceptive measures as required by local law or practice)
  • Known or suspected allergy to trial product(s) or related products
  • Any condition that the local investigator feels would interfere with trial participation or the evaluation of results
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02036372

Contacts
Contact: Jorinde AW Polderman, MD +31205669111 ext 57431 j.a.polderman@amc.uva.nl
Contact: Jeroen Hermanides, MD, PhD +31205669111 j.hermanides@amc.uva.nl

Locations
Netherlands
Academic Medical Center Amsterdam Recruiting
Amsterdam, Please Select, Netherlands, 1105AZ
Contact: Jorinde Polderman       j.a.polderman@amc.uva.nl   
Principal Investigator: Benedikt Preckel, MD, PhD         
Diakonessenhuis Recruiting
Utrecht, Netherlands, 3582 KE
Contact: Peter L Houweling, MD, PhD    088-2505000    phouweli@diakhuis.nl   
Sub-Investigator: Jorinde Polderman, MD         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Benedikt Preckel, MD, PhD Academic Medical Centre - AMC-UvA
  More Information

Additional Information:
No publications provided

Responsible Party: B Preckel, Prof dr B Preckel, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT02036372     History of Changes
Other Study ID Numbers: NL 41467.018.12
Study First Received: January 10, 2014
Last Updated: May 13, 2014
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
glucose
diabetes mellitus
perioperative

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014