Clinical trial NCT04803955: Efficacy and Safety of Kukoamine B Mesilate in Sepsis Patients
Official title: Efficacy and Safety of Kukoamine B Mesilate in Sepsis Patients: a Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 2 Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Sepsis
Lead sponsor: Tianjin Chasesun Pharmaceutical Co., LTD
Sponsor class: INDUSTRY
Collaborators: name: Southwest Hospital, China
First posted: 2021-03-18
Enrollment: 424
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase II study of Kukoamine B Mesilate in Sepsis Patients

Detailed description: To Assess Efficacy,Safety,Pharmacokinetics of Kukoamine B Mesilate in Sepsis Patients

Eligibility criteria: Inclusion Criteria:

* (1) The age of ≥ 18 years of age and ≤ 85 years of age, gender is not limited;
* (2) Meeting the diagnostic criteria for sepsis 3.0, i.e. sequential organ failure score (SOFA) increased by ≥2 points from baseline for patients with confirmed or suspected infection;
* (3) Confirmed or suspected bacterial infection (Pulmonary, abdominal，urinary system or hematogenous infections);
* (4) Infection-related organ failure does not exceed 48 hours; organ failure is defined as circulation, (SOFA) ≥ 3 points in at least one organ or system of the respiratory, kidney, liver, coagulation and central nervous system;
* (5) Childbearing age within six months without child care plan and agreed to take effective measures during the study of contraception;
* (6) Patients or guardians signed informed consent.

Exclusion Criteria:

* (1) Pregnancy or lactation women；
* (2) Patients are expected to live less than 48 hours;
* (3) Patients had poor control of malignant tumor, end-stage lung disease and other end-stage diseases, or had acardiac arrest，acute pulmonary embolism，blood transfusion response and acute coronary syndrome within 4 weeks prior to enrollment;
* (4) The patient has the following chronic organ dysfunction or immunosuppression (based on the chronic health scoring assessment of the APACHE II score) : 1) heart: New York heart association cardiac function IV; 2) breathing: chronic obstructive, obstructive, or vascular lung disease can lead to severe restrictions on activities, i.e. the inability to go upstairs or to do housework; Or clear chronic hypoxia, CO2 retention, secondary real erythrocyte, severe pulmonary hypertension (mPAP\> 40 mmHg) or respiratory muscle dependence; 3) kidneys: receiving long-term dialysis; 4) liver: liver cirrhosis confirmed by biopsy and clear portal hypertension; The upper digestive tract hemorrhage caused by portal hypertension; Or previous liver failure/hepatic encephalopathy/hepatic coma; 5) of immune function: accept the treatment of impact resistance to infection, such as immune suppression therapy, chemotherapy, radiotherapy or chemotherapy within 6 months, long-term (continuous use ≥3 weeks) use of glucocorticoids or recent (within 5 days before screening) cumulative use of prednisone or equivalent dose ≥100mg , or sickness impact resistance to infection, such as leukemia, lymphoma and AIDS);
* (5) Previous solid organ or bone marrow transplantation;
* (6) Plant survival status;
* (7) Confirmed or highly suspected of acute infectious diseases such as viral hepatitis activity , or clinically confirmed active tuberculosis;
* (8) Patients with sinus bradycardia (less than 60 per minute);
* (9) Uncontrolled bleeding in the past 24 hours（Clinical judgment requires transfusion support）;
* (10) Large area burns or chemical burns (III degree burns area \> 30% BSA);
* (11) The average arterial pressure was \< 65 mmHg after adequate liquid resuscitation and vasoactive drug therapy;
* (12) Acute myeloid hematopoiesis was characterized by a lack of severe granulocytes (ANC \< 500 / mm3);
* (13) Allergic to the active ingredient or its auxiliary materials;
* (14) The medication patients are using may severely affect the metabolism of the drug;
* (15) Patients and (or) guardians have signed a Do Not Rescue (DNR), or decided to withdraw life support (withdraw) or restrict life support for the intensity (withhold) and sign the informed consent form;
* (16) Participated in clinical intervention test in 3 months;
* (17) The subject is a researcher or his immediate family member, or may have improper informed consent;
* (18) The investigator considers it inappropriate for the patient to participate in this test.

Primary outcomes:
measure: Delta SOFA (ΔSOFA)
timeFrame: Day 8 after the first dose (Within 24 hours after the last dose on day 7)
Secondary outcomes:
measure: Clinical Outcome Composite Endpoint
timeFrame: 28 days after the first dose
measure: Proportion of patients with 7-day all-cause deaths
timeFrame: 7 days after the first dose
measure: Proportion of patients transferred out of ICU
timeFrame: 7 days after the first dose
measure: Quantification of IL-6
timeFrame: Day 2, 4 , 8 after the first dose (Within 24 hours after the last dose on day 7)
measure: Delta SOFA (ΔSOFA)
timeFrame: Day 1, 3, 5 after the first dose
measure: Duration of use and abstention of life support treatment
timeFrame: 28 days after the first dose
measure: Duration of ICU stay and absence
timeFrame: 28 days after the first dose
measure: Rate of adverse events/serious adverse events
timeFrame: From date of singing informed consent until the 29 days after the first dose
Other outcomes:
measure: Area under the curve at steady state (AUCss)
timeFrame: Day 1 and Day 7
measure: Peak plasma concentration at steady state (Cmaxss)
timeFrame: Day 1 and Day 7
measure: Trough plasma concentration at steady state (Cminss)
timeFrame: Day 1 and Day 7
measure: Correlation between the exposure of Kukoamine B Mesilate and its efficacy
timeFrame: Day 8 after the first dose (Within 24 hours after the last dose on day 7)
measure: Correlation between the exposure of Kukoamine B Mesilate and hepatic-related treatment-related adverse events
timeFrame: Day 1 to Day 8
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: