Multi-center Clinical Study of Early Antibios of Severe Acute Pancreatitis

Escalade or Deseacalade Antibiotic Use in Severe Acute Pancreatitis

Strategy of antibiotic therapy in SAP,De-escalate (cefoperazone+metronidazole) or Escalate (meropenem) therapy,which one is better.

Study Overview

• Status: Unknown
• Conditions: Pancreatitis,Acute Necrotizing
• Intervention / Treatment: Procedure: oral care by chlorhexidine gluconate; Procedure: enteral nutrition; Drug: Somatostatin; Drug: Meropenem; Drug: cefoperazone + metronidazole

Detailed Description

SAP is a serious and life-threatening disease and requires intensive and aggressive management of multiple organ failure and severe infectious complications that can develop in these patients. The most common cause of death in patients suffering from severe acute pancreatitis (SAP) is the infection of pancreatic necrosis by enteric bacteria with mortality rates of 30% (range 14- 62%),spurring the discussion of whether or not prophylactic antibiotic administration could be a beneficial approach. Pancreatic infections are more often monomicrobial, especially E. coli in the two first weeks (100% and 62.5%) of onset, with a shift from gram-negative to gram-positive as the pancreatitis progressed.

In order to evaluate the benefit of prophylactic antibiotic application, a number of randomized controlled clinical trials have been published over the past 15 years. Since the results were conflicting and most studies were of low methodological quality and/or statistically underpowered, meta-analyses have been performed to assess this important issue. However, their results ranged from absolutely no effect of antibiotic prophylaxis to positive effects regarding mortality, the incidence of infected pancreatic necrosis and the incidence of extra pancreatic infections.

In order to provide reliable evidence of the effect of antibiotherapy strategy in SAP, we performed a prospective randomized multicenter clinical trial.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Enqiang Mao, M.D; Phone Number: 86-13501747906

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Depatrment of EICU,Ruijin Hospital
      • Contact: Enqiang, Mao; Phone Number: 86-13501747906
      • Sub-Investigator: Zhitao Yang, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• severe Acute Pancreatitis according to Atlanta criteria revisited in 2012

Exclusion Criteria:

• concurrent sepsis or (peri)pancreatic infection caused by a second disease
• patients with chronic organ failure (chronic renal failure needs kidney replacement, chronic heart failure, decompensate hepatic cirrhosis, chronic obstructive pulmonary disease)
• recurrent or endoscopic retrograde cholangiopancreatography (ERCP), or traumatic or operative pancreatitis
• pregnancy, malignancy or immunodeficiency
• a history of allergy to meropenem, cefoperazone and metronidazole
• a history of antibiotic administration within 48 h prior to enrollment
• possible death within 48 h after enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: cefoperazone + metronidazole; cefoperaozone 2g q8h + MDZ 0.5g q8h Oral care Somatostatin 3-6mg per 24h enteral nutrition	Procedure: oral care by chlorhexidine gluconate; oral care by 0.2% chlorhexidine gluconate twice daily; Other Names: chlorhexidine gluconate; Procedure: enteral nutrition; Other Names: Enteral Nutritional Suspension(SP) by NUTRICIA; Drug: Somatostatin; Other Names: somatostatin by merk; Drug: Meropenem; All patients in cefo-group do not meet 1 of 3 laboratory parameter or image parameter or 2 of 3 clinical parameters. 1.Clinical parameters (2 of 3): 1)temperature<37.8℃ or 2)HR <100bpm or 3)SpO2 >95% 2.Laboratory parameters (3 of 3): 1)CRP or 2)PCT reduction 70% compared to zenith for 2 consecutive samples 3)WBC <12×10E9/L for 2 consecutive samples 3.Image parameter (1 of 1): liquid collection developed <30% compared to that of 72h
ACTIVE_COMPARATOR: meropenem; Meropenem 0.5g q6h or adapted with renal function. Oral care Somatostatin 3-6mg per 24h enteral nutrition	Procedure: oral care by chlorhexidine gluconate; oral care by 0.2% chlorhexidine gluconate twice daily; Other Names: chlorhexidine gluconate; Procedure: enteral nutrition; Other Names: Enteral Nutritional Suspension(SP) by NUTRICIA; Drug: Somatostatin; Other Names: somatostatin by merk; Drug: cefoperazone + metronidazole; 1.Clinical parameters (2 of 3): 1)temperature<37.8℃ or 2)HR <100bpm or 3)SpO2 >95% 2.Laboratory parameters (3 of 3): 1)CRP or 2)PCT reduction 70% compared to zenith for 2 consecutive samples 3)WBC <12×10E9/L for 2 consecutive samples 3.Image parameter (1 of 1): liquid collection developed <30% compared to that of 72h; Other Names: Metronidazole; Cefobid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
pancreatic or peripancreatic infection	28-day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cost of management of SAP		90-day
Microbiology resistance	sputum, urine and blood culture will be done once or twice per week if needed. bill or other culutre will be done when the patient is undergoing operation.	90-day

Collaborators and Investigators

• Sponsor: Erzhen Chen
• Collaborators: RenJi Hospital
• Investigators: Study Chair: Er-Zhen Chen, M.D. & Ph.D., Ruijin Hospital; Study Director: En-Qiang Mao, M.D. & Ph.D., Ruijin Hospital; Principal Investigator: Zhi-Tao Yang, M.D. & Ph.D., Ruijin Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ANTICIPATED): December 1, 2015
• Study Completion (ANTICIPATED): December 1, 2016

Study Registration Dates

• First Submitted: October 31, 2013
• First Submitted That Met QC Criteria: November 18, 2013
• First Posted (ESTIMATE): November 25, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): November 25, 2013
• Last Update Submitted That Met QC Criteria: November 18, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: meropenem; metronidazole; antibiothearpy strategy; cefoperazone
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Pancreatitis, Acute Necrotizing; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dermatologic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Disinfectants; Anti-Infective Agents, Urinary; Renal Agents; Metronidazole; Chlorhexidine; Meropenem; Chlorhexidine gluconate; Somatostatin; Cefoperazone; Sulperazone
• Other Study ID Numbers: SAP BUNDLE-ANTIBIOTICS; 12411950500 (Other Grant/Funding Number: Science and Technology Commission of Shanghai Municipality)