Ulinastatin Treatment in Adult Patients With Sepsis and Septic Shock in China

NCT02647554 | Completed Phase 4 DMC

• 1 other identifier: UTI-S001
• Study Type: interventional
• Target: 347
• Locations: 1 country
• Sites: 1

Brief Summary

A Prospective, Multi-Centre, Double-Blind, Randomized, Placebo-Controlled, Trial of Ulinastatin Treatment in Adult Patients with Sepsis and Septic Shock in China

Conditions

Sepsis; Septic Shock

Keywords

sepsis; septic shock; Ulinastatin; adult; China

Outcome Measures

Primary Outcomes (1)

• all cause mortality

  death from all causes at 28-days

  28 days

Secondary Outcomes (22)

• mortality

  90 days

• mortality in ICU

  through ICU discharge, an average of 14 days

• mortality rate at hospital discharge

  through hospital discharge, an average of 21 days

• ICU-free days

  28 days

• SOFA score

  Day 1,3,6,10,14,28 after randomization

Study Arms (2)

Ulinastatin group

EXPERIMENTAL

Ulinastain treatment group：400,000 IU ulinastatin will be reconstituted in 10 mL of 0.9% normal saline, and then dissolved in 100 mL of 0.9% normal saline every 8 hours for 10 days in a double-blind fashion.

Drug: ulinastatin

Placebo group

PLACEBO COMPARATOR

Placebo control group：Matching with medication

Drug: Placebo

Interventions

ulinastatin DRUG

ulinastatin 400,000 IU every 8 hours for 10 days

Also known as: urinary trypsin inhibitor

Ulinastatin group

Placebo DRUG

matching placebo every 8 hours for 10 days

Placebo group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Sepsis-3 criteria from Society of Critical Care Medicine (SCCM) /European Society of Intensive Care Medicine(ESICM)
• Suspected or confirmed infection AND
• Evidence of acute organ dysfunction • in patients not known to have preexisting organ dysfunction (The baseline SOFA score can be assumed to be zero): total SOFA score ≥2 points from 48 hours before infection to 24 hours after infection.
• in patients known to have preexisting organ dysfunction (The baseline SOFA score can be assumed according to baseline conditions): changes of total SOFA score ≥2 points from 48 hours before infection to 24 hours after infection.
• ）48 hours within diagnosis of sepsis 3）Signed and dated informed consent should be obtained prior to any screening procedures from subjects (or legal representatives). If the subject is unable to provide consent, it could be obtained from legal representatives according to local regulation. Consent from subject should be obtained afterwards when available.
• ） Fertile men or women should agree to use efficient birth control methods during the treatment period and at least 28 days after last dose. Fertile is defined as biologically fertile and sexually active from investigator's view.
• ） Non-childbearing women (meet at least one of following criteria):
• Past hysterectomy or bilateral oothectomy；
• Medically confirmed ovarian failure, or menopause (amenorrhea for 12 month or more and with no other pathological or physiological reason)

You may not qualify if:

• \) Age \< 18 years, or age\>80 years 2) Pregnancy or lactating 3) New York Heart Association Class IV congestive heart failure, nonseptic cardiogenic shock, or uncontrolled acute blood loss 4) Severe, preexisting, parenchymal liver disease with clinically significant portal hypertension, Child-Pugh C stage cirrhosis or acute liver failure 5) Receipt of a solid-organ or bone marrow transplant 6) Advanced pulmonary fibrosis or non invasive ventilation before study entry 7) Myocardial infarction within the previous 3 months 8) Cardiopulmonary resuscitation within 72 hours before study entry 9） Invasive fungal infection or active pulmonary tuberculosis 10) Full-thickness thermal or chemical burn involving 30% or more of body surface area 11) Evidence of significant drug- or disease-induced immunosuppression
• · Evidence of moderate or severe neutropenia, i.e. absolute neutrophil count (ANC) \< 1.0 x 10\^9/L
• Administration of high doses of corticosteroids, i.e. doses of \> 20 mg/day of prednisone or equivalent, for ≥ 2 weeks immediately prior to evaluation for enrollment. Hydrocortisone at dose ≤ 300 mg/d for treatment of septic shock is acceptable.
• Immunomodulatory medication (e.g. cyclosporine, azathioprine, OKT3), chemotherapy, or radiation therapy within 2 months before study entry
• Known HIV seropositivity
• Any disease sufficiently advanced to suppress resistance to infection
• Non-remission stage of hematological/lymphoid tumor 12) Previous Xuebijing, thymosin or IVIG Within 2 months before study entry 12) Inability to obtain informed consent or assent 13) Participation in an investigational clinical trial within 6 months of screening 14) Expected survival \< 2 months or chronic vegetative state 15) Lack of commitment to full, aggressive, life support 16) History of hypersensitivity to ulinastatin or any excipients or preservatives

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Techpool Bio-Pharma Co., Ltd.: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Location

Related Publications (16)

• Chalfin DB, Holbein ME, Fein AM, Carlon GC. Cost-effectiveness of monoclonal antibodies to gram-negative endotoxin in the treatment of gram-negative sepsis in ICU patients. JAMA. 1993 Jan 13;269(2):249-54.

  PMID: 8417245 BACKGROUND

• Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. doi: 10.1097/00003246-200107000-00002.

  PMID: 11445675 BACKGROUND

• Finfer S, Bellomo R, Lipman J, French C, Dobb G, Myburgh J. Adult-population incidence of severe sepsis in Australian and New Zealand intensive care units. Intensive Care Med. 2004 Apr;30(4):589-96. doi: 10.1007/s00134-004-2157-0. Epub 2004 Feb 12.

  PMID: 14963646 BACKGROUND

• Padkin A, Goldfrad C, Brady AR, Young D, Black N, Rowan K. Epidemiology of severe sepsis occurring in the first 24 hrs in intensive care units in England, Wales, and Northern Ireland. Crit Care Med. 2003 Sep;31(9):2332-8. doi: 10.1097/01.CCM.0000085141.75513.2B.

  PMID: 14501964 BACKGROUND

• Brun-Buisson C, Meshaka P, Pinton P, Vallet B; EPISEPSIS Study Group. EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units. Intensive Care Med. 2004 Apr;30(4):580-8. doi: 10.1007/s00134-003-2121-4. Epub 2004 Mar 2.

  PMID: 14997295 BACKGROUND

• Cheng B, Xie G, Yao S, Wu X, Guo Q, Gu M, Fang Q, Xu Q, Wang D, Jin Y, Yuan S, Wang J, Du Z, Sun Y, Fang X. Epidemiology of severe sepsis in critically ill surgical patients in ten university hospitals in China. Crit Care Med. 2007 Nov;35(11):2538-46. doi: 10.1097/01.CCM.0000284492.30800.00.

  PMID: 17828034 BACKGROUND

• Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013 Nov 21;369(21):2063. doi: 10.1056/NEJMc1312359. No abstract available.

  PMID: 24256390 BACKGROUND

• Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb S, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including The Pediatric Subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013 Feb;39(2):165-228. doi: 10.1007/s00134-012-2769-8. Epub 2013 Jan 30.

  PMID: 23361625 BACKGROUND

• Christaki E, Anyfanti P, Opal SM. Immunomodulatory therapy for sepsis: an update. Expert Rev Anti Infect Ther. 2011 Nov;9(11):1013-33. doi: 10.1586/eri.11.122.

  PMID: 22029521 BACKGROUND

• Sharony R, Yu PJ, Park J, Galloway AC, Mignatti P, Pintucci G. Protein targets of inflammatory serine proteases and cardiovascular disease. J Inflamm (Lond). 2010 Aug 30;7:45. doi: 10.1186/1476-9255-7-45.

  PMID: 20804552 BACKGROUND

• Inoue K, Takano H, Yanagisawa R, Yoshikawa T. Protective effects of urinary trypsin inhibitor on systemic inflammatory response induced by lipopolysaccharide. J Clin Biochem Nutr. 2008 Nov;43(3):139-42. doi: 10.3164/jcbn.2008059. Epub 2008 Oct 31.

  PMID: 19015747 BACKGROUND

• Huang N, Wang F, Wang Y, Hou J, Li J, Deng X. Ulinastatin improves survival of septic mice by suppressing inflammatory response and lymphocyte apoptosis. J Surg Res. 2013 Jun 15;182(2):296-302. doi: 10.1016/j.jss.2012.10.043. Epub 2012 Nov 9.

  PMID: 23158408 BACKGROUND

• Shao YM, Zhang LQ, Deng LH, Yao HG. [Clinical study on effects of ulinastatin on patients with systemic inflammatory response syndrome]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2005 Apr;17(4):228-30. Chinese.

  PMID: 15836828 BACKGROUND

• Karnad DR, Bhadade R, Verma PK, Moulick ND, Daga MK, Chafekar ND, Iyer S. Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in severe sepsis: a multicenter randomized controlled study. Intensive Care Med. 2014 Jun;40(6):830-8. doi: 10.1007/s00134-014-3278-8. Epub 2014 Apr 16.

  PMID: 24737258 BACKGROUND

• Yuhara H, Ogawa M, Kawaguchi Y, Igarashi M, Shimosegawa T, Mine T. Pharmacologic prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis: protease inhibitors and NSAIDs in a meta-analysis. J Gastroenterol. 2014 Mar;49(3):388-99. doi: 10.1007/s00535-013-0834-x. Epub 2013 May 30.

  PMID: 23720090 BACKGROUND

• Jiang W, Yu X, Sun T, Chai Y, Chang P, Chen Z, Pan J, Peng Z, Wang R, Wang X, Xu Y, Yu L, Zheng Q, Du B; China Critical Care Clinical Trials Group (CCCCTG). ADJunctive Ulinastatin in Sepsis Treatment in China (ADJUST study): study protocol for a randomized controlled trial. Trials. 2018 Feb 21;19(1):133. doi: 10.1186/s13063-018-2513-y.

  PMID: 29467017 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

urinastatin

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Bin Du, MD

  Peking Union Medical College Hospital, Beijing, China

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Medical ICU

Study Record Dates

• First Submitted: December 27, 2015
• First Posted: January 6, 2016
• Study Start: December 1, 2016
• Primary Completion: May 1, 2021
• Study Completion: August 1, 2021
• Last Updated: October 13, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)