Intensive Insulin for Severe/Moderate Hypertriglyceridemia Pancreatitis. (HAPinsulin)

Randomized, Controlled, Open-label Trial of Intravenous Intensive Insulin for Severe/Moderate Hypertriglyceridemia Pancreatitis.

The aim of this study is to investigate the therapeutic efficacy of intensive insulin in patients with hypertriglyceridemia induced moderate/severe acute pancreatitis on the course and outcome of disease.

Study Overview

• Status: Unknown
• Conditions: Hypertriglyceridemia; Acute Pancreatitis
• Intervention / Treatment: Drug: Insulin; Device: plasmapheresis

Detailed Description

Hypertriglyceridemia-induced acute pancreatitis occurs in about 1-4% of the cases. It is the third leading cause of pancreatitis after biliary and alcoholic etiology. Hypertriglyceridemia can be caused by primary causes, lipid metabolism disorders and secondary causes.

Hyperlipidemic pancreatitis can be provoked when triglyceride levels (TGL) exceed 11.3 mmol/l (1,000 mg/dl). Except for standard symptomatic treatment, plasmapheresis and insulin have been performed to rapidly reduce TGL and chylomicron levels in the blood.The therapeutic efficacy of intensive insulin, standard insulin, and plasmapheresis in patients with hypertriglyceridemia induced moderate/severe acute pancreatitis on the course and outcome of disease.After acceptance patients will be randomized by random envelope in the 3 groups: Group A: intensive insulin (glycemic control 4.4-6.1mmol/L), Group B: standard insulin (glycemic control 7.8-10.0 mmol/L), and Group C: plasmapheresis.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of hypertriglyceridemia induced acute pancreatitis (AP): Typical pain increase in serum lipase or amylase with serum TG> 1,000 mg/dL (11.3mmol/L) or serum was milky with serum TG> 500 mg/dL(5.65 mmol/L)
• Onset of abdominal pain within <=48h before admission
• moderate severe or severe Acute Pancreatitis according to Atlanta criteria
• except for other AP causes, such as cholelithiasis, alcohol, drugs and so on

Exclusion Criteria:

• other etiologies other than hyperlipidemia leading to AP
• at the same time combined with other etiologies of AP
• appear difficult to reverse respiratory failure, severe systemic circulatory failure, coma and other the endangered symptoms, patients expected to die within 24hours
• disseminated intravascular coagulation, or patients with severe active bleeding
• without informed consent, the patient refused to plasma replacement, and other circumstances may bring significant bias.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: intensive insulin; Group A: intensive insulin (glycemic control 4.4-6.1mmol/L)	Drug: Insulin; Group A: intensive insulin (glycemic control 4.4-6.1mmol/L), Group B: standard insulin (glycemic control 7.8-10.0 mmol/L), and Group C: plasmapheresis. Insulin was injected by insulin pump.
Active Comparator: Group B: standard insulin; Group B: standard insulin (glycemic control 7.8-10.0 mmol/L),	Drug: Insulin; Group A: intensive insulin (glycemic control 4.4-6.1mmol/L), Group B: standard insulin (glycemic control 7.8-10.0 mmol/L), and Group C: plasmapheresis. Insulin was injected by insulin pump.
Active Comparator: Group C: plasmapheresis	Device: plasmapheresis; Triglyceridemia should be less than 5.65 mmol/l.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of mortality	Number of participants with fatal outcome during hospitalisation	From admition to hospital discharge, an average of 2 months
Reduction of organ failure	reanl failure, respiratory failure, circulatory failure etal	From admition to hospital discharge, an average of 2 months
triglyceride levels	triglyceride levels	From admition to hospital discharge, an average of 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cytokines in serum, urine	IL-6, IL-8, IL-10	From admition to 7 days
insulin dose	insulin dose	From admition to 7 days
Severity Score in CT scan	CT Balthazar score/grade or MCTSI score	From admition to 7 days
TNF-α in serum, urine	TNF-α	From admition to 7 days
Clinical Severity Score	BISAP score	From admition to 7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genomics	cfDNA et.al.	From admition to 7 days
Clinical Severity Score	Ranson score	From admition to 7 days
Clinical Severity Score	Apache2	From admition to 7 days

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Wenzhou Medical University
• Investigators: Study Director: Meng-Tao Zhou, M.D., The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

Publications and helpful links

General Publications

• Lutfi R, Huang J, Wong HR. Plasmapheresis to treat hypertriglyceridemia in a child with diabetic ketoacidosis and pancreatitis. Pediatrics. 2012 Jan;129(1):e195-8. doi: 10.1542/peds.2011-0217. Epub 2011 Dec 26.
• Tsuang W, Navaneethan U, Ruiz L, Palascak JB, Gelrud A. Hypertriglyceridemic pancreatitis: presentation and management. Am J Gastroenterol. 2009 Apr;104(4):984-91. doi: 10.1038/ajg.2009.27. Epub 2009 Mar 17.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 6, 2018
• Primary Completion (Anticipated): March 8, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: March 29, 2018
• First Submitted That Met QC Criteria: April 10, 2018
• First Posted (Actual): April 18, 2018

Study Record Updates

• Last Update Posted (Actual): June 6, 2018
• Last Update Submitted That Met QC Criteria: June 4, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: insulin; Plasmapheresis; hyperlipidaemic pancreatitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Pancreatic Diseases; Pancreatitis; Hypertriglyceridemia; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: HAPinsulin

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes