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

Study Overview
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Brief Summary
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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).

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

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

Conditions
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Acute Lung Injury, Sepsis

Intervention / Treatment
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* Drug: Huzhangxiefei Decoction
* Drug: 10% Huzhangxiefei Decoction


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute lung injury, sepsis, Chinese Traditional Medicine, Chinese Herbal Drugs, acute respiratory distress syndrome