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

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

Detailed Description
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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.

Official Title
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Escalade or Deseacalade Antibiotic Use in Severe Acute Pancreatitis

Conditions
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Pancreatitis,Acute Necrotizing

Intervention / Treatment
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* Drug: cefoperazone + metronidazole
* Procedure: oral care by chlorhexidine gluconate
* Procedure: enteral nutrition
* Drug: Somatostatin
* Drug: Meropenem


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cefoperazone + metronidazole<br>cefoperaozone 2g q8h + MDZ 0.5g q8h Oral care Somatostatin 3-6mg per 24h enteral nutrition | Procedure: oral care by chlorhexidine gluconate<br>* oral care by 0.2% chlorhexidine gluconate twice daily<br>* Other names: chlorhexidine gluconate;Procedure: enteral nutrition<br> <br> * Other names: Enteral Nutritional Suspension(SP) by NUTRICIA;Drug: Somatostatin<br> <br> * Other names: somatostatin by merk;Drug: Meropenem<br>* 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<br>|
| Active Comparator: meropenem<br>Meropenem 0.5g q6h or adapted with renal function. Oral care Somatostatin 3-6mg per 24h enteral nutrition | Drug: cefoperazone + metronidazole<br>* 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<br>* Other names: Metronidazole;Procedure: oral care by chlorhexidine gluconate<br>* oral care by 0.2% chlorhexidine gluconate twice daily<br>* Other names: chlorhexidine gluconate;Procedure: enteral nutrition<br> <br> * Other names: Enteral Nutritional Suspension(SP) by NUTRICIA;Drug: Somatostatin<br> <br> * Other names: somatostatin by merk;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibiothearpy strategy, cefoperazone, metronidazole, meropenem