Use of Streptokinase for Enhancement of Percutaneous Drainage of Pancreatic Necrosis

Acute Pancreatitis Clinical Trial

Official title:

Phase 2/3 Study of Use of Streptokinase for Enhancement of Percutaneous Drainage of Pancreatic Necrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01977118
• Other study ID #: NK/1180/M.CH
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 23, 2013
• Last updated: July 5, 2016
• Start date: May 2013
• Est. completion date: December 2014

Study information

• Verified date: July 2016
• Source: Postgraduate Institute of Medical Education and Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: PostGraduate Institute of Medical Education and Research
• Study type: Interventional

Clinical Trial Summary

Around 20 per cent of patients with acute pancreatitis develop pancreatic or peripancreatic necrosis with or without peripancreatic collection.

Percutaneous catheter drainage successfully drains the liquefied component of pancreatic necrosis while the solid component still remains undrained. This infected solid component of pancreatic necrosis is probably responsible for failure of percutaneous catheter drainage which demands surgical debridement.

Streptokinase is a protein secreted by several species of streptococci which can bind and activate human plasminogen.

In the present study investigators plan to instill streptokinase locally in to the collections of patients with severe acute pancreatitis via pigtail catheter inorder to liquefy the solid necrotic component and analyze whether it hastens the drainage and thereby delays or obviates the need for necrosectomy.

Description:

Around 20 per cent of patients with acute pancreatitis develop pancreatic or peripancreatic necrosis with or without peripancreatic collections. Sterile necrosis can generally be managed conservatively and the mortality rate is relatively low (12 per cent). Approximately 30 (range 14-62) per cent of patients with necrotizing pancreatitis, however, develop secondary infections of peripancreatic fluid collection which is associated with sepsis and organ failure and is an indication for intervention1.

Until recently, the first-choice intervention in patients with infected necrotizing pancreatitis or sterile necrosis with clinical deterioration (multiple organ failure) has been open surgical necrosectomy. This approach is associated with considerable morbidity (34-95 per cent) and mortality (11-39 per cent). In 1998, Freeny and colleagues10 first described a consecutive series of patients with infected pancreatic necrosis who were treated primarily with imaging-guided percutaneous catheter drainage (PCD), as an alternative to primary surgical necrosectomy. The rationale for PCD was to drain the infected fluid under tension and gain time to improve organ function of these critically ill patients and thereby delay or avoid surgical necrosectomy. In their retrospective cohort study, PCD was successful in postponing surgical intervention for a median of 4 weeks and even obviated the need for surgical necrosectomy in almost half of the patients. In addition, PCD seems technically feasible in the vast majority of patients with necrotizing pancreatitis.

In clinical experience, investigators have found that PCD successfully drains the liquefied component of pancreatic necrosis while the solid component still remains undrained. This infected solid component of pancreatic necrosis is probably responsible for failure of PCD which demands surgical debridement.

Streptokinase is a protein secreted by several species of streptococci which can bind and activate human plasminogen. It is primarily used in clinical practice intravenously as an effective thrombolytic agent in cases of myocardial infarction and pulmonary thromboembolism.

The earliest reports on intracavitatory use of Streptokinase and other fibrinolytics were for empyemas. Later because of beneficial results, their intracavitatory use was extended to other conditions like liver, retroperitoneal and peritoneal abscesses.

In a phase II study, intracavitatory urokinase has shown to facilitate percutaneous drainage significantly reduce hospital stay and costs of percutaneous drainage of intra abdominal, retroperitoneal abscesses.

In the present study investigators plan to instill streptokinase locally in to the collections of patients with severe acute pancreatitis via pigtail catheter inorder to liquefy the solid necrotic component and analyze whether it hastens the drainage and thereby delays or obviates the need for necrosectomy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients with severe acute pancreatitis managed by percutaneous catheter drainage

Exclusion Criteria:

• An acute intra abdominal event (perforation of hollow viscus, bleeding, or abdominal compartment syndrome) before or after PCD insertion.

• Previous drainage or surgical necrosectomy for infected pancreatic necrosis (ERCP with or without papillotomy is allowed.)

• Previous exploratory laparotomy for acute abdomen and diagnosis of pancreatitis during laparotomy

• Patients who are allergic to streptokinase.

• Patients with deranged coagulation profile.

• Patients with recent history of cerebrovascular accident [< 2 months], intracranial or intraspinal surgery, uncontrolled hypertension, intracranial neoplasm.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Pancreatitis
• Necrosis
• Pancreatitis

Intervention

Drug:
• streptokinase
50000U of injection streptokinase dissolved in 100ml of diluent instilled in to the pancreatic and/or peripancreatic collections via percutaneous catheters and clamped for 2 hours in Streptokinase group. After release of clamp, cavity will be irrigated with 100-500ml of saline. This procedure will be performed thrice daily for five days.

Other:
• Saline irrigation
100 ml of normal saline will be instilled through percutaneous catheters in the pancreatic and/or peripancreatic collections and clamped for 2 hours. After release of clamp, cavity will be irrigated with 100-500ml of saline. This procedure will be performed thrice daily for five days

Locations

Country	Name	City	State
India	Postgraduate Institute of Medical Education and Research	Chandigarh

Sponsors (1)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sepsis reversal		From date of randomization until the date of necrosectomy, discharge or death from any cause, whichever came first, assessed upto 1 month	No
Primary	Mortality		From the date of randomization until last follow up after discharge, assessed up to 1 month	Yes
Secondary	Length of intensive care unit (ICU) and hospital stay		From date of randomization until the date of discharge or death from any cause, whichever came first, assessed upto 1 month	No
Secondary	Proportion of patients requiring surgical necrosectomy		From date of randomization until the date of discharge or death from any cause, whichever came first, assessed upto 1 month	No
Secondary	Number and size of catheters required		From date of first pigtail insertion until the date of necrosectomy, discharge or death from any cause, whichever came first, assessed upto 1 month	No
Secondary	Number of interventions required		From date of first pigtail insertion until the date of necrosectomy, discharge or death from any cause, whichever came first, assessed upto 1 month	No
Secondary	Catheter-related complications		From date of first pigtail insertion until the date of necrosectomy, discharge or death from any cause, whichever came first, assessed upto 1 month	Yes
Secondary	Streptokinase related complications		From date of randomization until the date of necrosectomy, discharge or death from any cause, whichever came first, assessed upto 1 month	Yes