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

Sponsor

Erzhen Chen (Other)

Overall Status

Unknown status

CT.gov ID

NCT01992198

Collaborator

RenJi Hospital (Other)

Enrollment

Location

Arms

Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pancreatitis,Acute Necrotizing	Drug: cefoperazone + metronidazole Procedure: oral care by chlorhexidine gluconate Procedure: enteral nutrition Drug: Somatostatin Drug: Meropenem	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Escalade or Deseacalade Antibiotic Use in Severe Acute Pancreatitis

Study Start Date :

Jul 1, 2012

Anticipated Primary Completion Date :

Dec 1, 2015

Anticipated Study Completion Date :

Dec 1, 2016

Arms and Interventions

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	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: Cefobid Metronidazole 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

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

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:

Cefobid

Metronidazole

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

Outcome Measures

Primary Outcome Measures

pancreatic or peripancreatic infection [28-day]

Secondary Outcome Measures

cost of management of SAP [90-day]
Microbiology resistance [90-day]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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