Oral Administration or Nasal Feeding of Huzhangxiefei Decoction for Treatment in Sepsis Induced Acute Lung Injury

Hypothesis 1A: Oral Administration or Nasal Feeding of Huzhangxiefei Decoction will significantly attenuate sepsis-induced systemic organ failure as measured by overall response rate.

Hypothesis 1B: Oral Administration or Nasal Feeding of Huzhangxiefei Decoction will attenuate sepsis-induced lung injury as assessed by the respiratory rate and oxygenation index.

Hypothesis 1C: Oral Administration or Nasal Feeding of Huzhangxiefei Decoction will attenuate sepsis-induced lung injury as assessed by chest x-ray scale score, Chinese Medicine scale score.

Hypothesis 1D: Oral Administration or Nasal Feeding of Huzhangxiefei Decoction will attenuate biomarkers of inflammation (C-Reactive Protein, Procalcitonin), vascular injury (Thrombomodulin, Angiopoietin-2), alveolar epithelial injury (Receptor for Advanced Glycation Products), while inducing the onset of a fibrinolytic state (Tissue Factor Pathway Inhibitor).

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Acute Lung Injury
• Intervention / Treatment: Drug: Huzhangxiefei Decoction; Drug: 10% Huzhangxiefei Decoction

Detailed Description

Huzhangxiefei Decoction is a prescription formulated by a professional doctor of traditional Chinese medicine

• Study Type: Interventional
• Enrollment (Anticipated): 58
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Li Xiang, graduate; Phone Number: 86-18555504579; Email: 1438325179@qq.com

Study Locations

• China
  • Shanghai, China, 200092
    • Recruiting
    • ShanghaiXinhua
    • Contact: Li Xiang, graduate; Phone Number: 86-18555504579; Email: 1438325179@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have suspected or proven infection, and be accompanied by at least 1 criterion for sepsis-induced organ dysfunction, and meet all 5 criteria for Acute Respiratory Distress Syndrome (ARDS).

Suspected or proven infection: (e.g., thorax, urinary tract, abdomen, skin, sinuses, central venous catheters, and central nervous system).

The presence of sepsis associated organ dysfunction: (any of the following thought to be due to infection): Sepsis associated hypotension (systolic blood pressure (SBP) < 90 mm Hg or an SBP decrease > 40 mm Hg unexplained by other causes or use of vasopressors for blood pressure support (epinephrine, norepinephrine, dopamine =/> 5mcg, phenylephrine, vasopressin); Arterial hypoxemia (PaO2/FiO2 < 300) or supplemental O2 > 6LPM; Lactate > upper limits of normal laboratory results; Urine output < 0.5 ml/kg/hour for > two hours despite adequate fluid resuscitation; Platelet count < 100,000 per mcL; Coagulopathy (INR > 1.5); Bilirubin > 2 mg/dL; Glasgow Coma Scale < 11 or a positive CAM ICU score.

ARDS characterized by all the following criteria Lung injury of acute onset, within 1 week of an apparent clinical insult and with progression of respiratory symptoms Bilateral opacities on chest imaging not explained by other pulmonary pathology (e.g. pleural effusions, lung collapse, or nodules) Respiratory failure not explained by heart failure or volume overload Decreased arterial PaO2/FiO2 ratio ≤ 300 mm Hg Minimum PEEP of 5 cmH2O (may be delivered noninvasively with CPAP to diagnose mild ARDS

Exclusion Criteria:

• inability to obtain consent;
• age < 18 years;
• pregnancy or breast feeding;
• moribund patient not expected to survive 24 hours;
• for patients with chronic liver insufficiency, renal insufficiency, blood system disease, etc., it is impossible to judge that the organ insufficiency occurred after this infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Huzhangxiefei Decoction; Huzhangxiefei Decoction, 50ml, Oral Administered or Nasal Feeding 5 minutes after breakfast and dinner for 7 days	Drug: Huzhangxiefei Decoction; Huzhangxiefei Decoction, 50ml, Oral Administered or Nasal Feeding 5 minutes after breakfast and dinner for 7 days
Placebo Comparator: 10% Huzhangxiefei Decoction; 10% Huzhangxiefei Decoction, 50ml, Oral Administered or Nasal Feeding of 5 minutes after breakfast and dinner for 7 days	Drug: 10% Huzhangxiefei Decoction; 10% Huzhangxiefei Decoction, 50ml, Oral Administered or Nasal Feeding 5 minutes after breakfast and dinner for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sequential Organ Failure Assessment (SOFA) Score	SOFA is a single score based on patient status of five different biological systems: respiratory, cardiovascular, coagulation, renal, and neurological. Scores range from 0 to 24 with higher scores indicated worse status	up to 7 days
C-Reactive Protein at Study Hours 0, 96, 168 When Compared to Placebo	C-Reactive Protein at Study Hours 0, 96, 168 When Compared to Placebo	up to 168 hours
Oxygenation Index (FiO2 x Mean Airway Pressure/PaO2) at Study Hour 0, 96, 168 if Still Intubated in Oral Administration or Nasal Feeding of Huzhangxiefei decoction Patient Compared to Placebo	Oxygenation Index (FiO2 x Mean Airway Pressure/PaO2) at Study Hour 0, 96, 168 if Still Intubated in Oral Administration or Nasal Feeding of Huzhangxiefei decoction Patient Compared to Placebo	up to 168 hours
overall response rate	Overall response rate=(the number of marked response patients+the number of moderate response)/the number of all patients within group Four criteria were established as follows: RR(d1)-RR(d7)≥5 breaths per minute or 12 breaths per minute≤RR(d7)≤20breaths per minute; OI(d7)-OI(d1)≥50mmHg; [CXSS(d1)-CXSS(d7)]/CXSS(d1)≥10%; CMSS(d1)-CMSS(d7)≥3 points Marked response: three or four criteria of the above are met Moderate response：two criteria of the above are met No response: none or only one criterion of the above is met RR refers to respiratory rate, breaths per minute OI refers to oxygenation index, mmHg CXSS refers to chest x-ray scale score CMSS refers to Chinese Medicine scale score	up to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator Free Days to Day 28	Ventilator Free Days to Day 28	Up to Day 28
ICU-free Days at Day 28	ICU-free Days at Day 28	Up to Day 28
All Cause Mortality to Day 28	All Cause Mortality to Day 28	Up to Day 28
Hospital-free Days at Day 60	Hospital-free Days at Day 60	Up to Day 60
Procalcitonin at Study Hour 0, 96, 168	Procalcitonin at Study Hour 0, 96, 168	Up to hour 168
Tissue Factor Pathway Inhibitor at Study Hour 0, 96, 168	Tissue Factor Pathway Inhibitor at Study Hour 0, 96, 168	Up to hour 168
Oxygenation Score: Pressure	Oxygenation as measure by the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2). Scores range from 100 to 300 with lower values indicating more worse outcomes	Up to hour 168
Coagulation	Coagulation as measured by Platelets per unit of blood. Scores range from less than 20 to more than 150. Lower scores indicate worse outcomes	Up to hour 168
Liver Function	Liver function as measured by Total Bilirubin	Up to hour 168
Cardiovascular Function	Cardiovascular function as measured by Mean arterial pressure. Scores less than 70 mmHg indicate worse outcomes.	Up to hour 168
State of Consciousness	State of consciousness as measure by Glasgow Coma Scale which gives a score based on eye, verbal, and motor responses. Scores range from 3 to 15 with lower scores indicating worse outcome	Up to hour 168
Renal Function	Renal function as measured by Creatinine.	Up to hour 168

Collaborators and Investigators

• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2021
• Primary Completion (Anticipated): November 30, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: June 24, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): June 25, 2021

Study Record Updates

• Last Update Posted (Actual): November 26, 2021
• Last Update Submitted That Met QC Criteria: November 23, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: sepsis; acute lung injury; acute respiratory distress syndrome; Chinese Herbal Drugs; Chinese Traditional Medicine
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Diseases; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Thoracic Injuries; Sepsis; Toxemia; Wounds and Injuries; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: XH-21-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No