Severe Acute Pancreatitis
Conditions
Keywords
high-dose intravenous vitamin C, severe acute pancreatitis
Brief summary
This study is a prospective, randomized, double-blinded, parallel-controlled, multi-central clinical trial for patients with severe acute pancreatitis (SAP). Patients with SAP in the early stage (within 7 days of onset) and over the age of 18, based on the routine treatment, will be randomly divided into a high-dose intravenous vitamin C group (HDIVC, 500mg/kg/24h, administered by iv. pump at a rate of 2g/h for 7 days) and a control group (an equal volume of normal saline). The primary endpoint is mortality rate in ICU, and secondary endpoints include free organ support duration (FOSD) within 14 days after enrollment, changes in inflammatory response and severity, disease severity scores and changes, fluid retention, incidence of infectious pancreatic necrosis (IPN), ICU mortality, pancreatic necrosis scores, monitoring of vitamin C plasma concentrations before and after HDIVC use, composition of gut microbiota, observation of vitamin C-related adverse reactions. The study hypothesis is that HDIVC can reduce mortality rate in ICU, significantly decrease the FOSD within 14 days and significantly reduce inflammatory response, decrease fluid retention, and improve disease severity.
Interventions
DRUGSaline (NaCl 0,9 %)
The control group involves only adding 50ml of normal saline to a 50ml syringe, without any labels to ensure identical appearance, and the method of administration and dosage are the same with vitamin C group.
Vitamin C at dose of 500mg/kg/24h, 2g/h
Sponsors
Shanghai Municipal Science and Technology Commission
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Time from onset of illness to enrollment is less than 7 days * Meet the 2012 Atlanta Guidelines SAP diagnostic criteria
Exclusion criteria
* SAP caused by tumors or ERCP * Pregnant or breastfeeding * Allergic to vitamin C * Use of other experimental drugs within the timeframe of this study * Chronic organs failure such as heart, liver, lung, or kidney before admission, with specific indicators being (chronic cardiovascular dysfunction requiring long-term mechanical hemodynamic support or inotropic drug support; chronic obstructive pulmonary disease requiring home oxygen therapy; chronic liver dysfunction at Child-Pugh Class C; chronic kidney disease with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m² or serum creatinine greater than 150 μmol/L) * Immunosuppressed state, including malignant tumors, post-transplant status, long-term use of immunosuppressor (for at least 1 month before enrollment), AIDS, etc. * The patient and family are unwilling to sign the informed consent form * Body weight greater than 100kg * Urinary system stones
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mortality rate in ICU | through study completion, an average of 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Impact of HDIVC on Early Inflammatory Markers in SAP, Including the Levels and Changes of C-Reactive Protein and Inflammatory Cytokines IL-6, IL-1, and IL-10 | 28 days of enrollment | — |
| the Duration of Systemic Inflammatory Response Syndrome (SIRS) | 28 days of enrollment | The scoring system primarily includes the following four clinical indicators. If ≥2 criteria are met, SIRS can be diagnosed: 1. Temperature \>38°C or \<36°C 2. Heart Rate\>90 beats per minute 3. Respiratory rate \>20 breaths per minute, or arterial PaCO₂ \<32 mmHg 4. Abnormal White Blood Cell (WBC) Count \>12×10⁹/L or \<4×10⁹/L, or immature neutrophils \>10% |
| The Impact of HDIVC on Sequential Organ Failure Assessment (SOFA) Score | 28 days of enrollment | The SOFA score involves six major organ systems, including the respiratory system, hematologic system (platelets), liver function, renal function, central nervous system, and circulatory system (blood pressure). Each system is scored from 0 to 4, with a total score ranging from 0 to 24. Higher scores indicate that the organ failure is more severe. |
| The Impact of HDIVC on Modified Marshall Score | 28 days of enrollment | This scoring system primarily evaluates three key organ systems (respiratory system, circulatory system and renal function), with each system scored from 0 to 4. If any system scores ≥2, organ dysfunction is considered present. |
| The Impact of HDIVC on Fluid Retention | 28 days of enrollment | assessment of fluid retention, defined as the total input volume of intravenous fluid and enteral nutrition minus the output volume of urine and drainage |
| The Impact of HDIVC on Acute Physiology and Chronic Health Evaluation II (APACHE II) Score | 28 days of enrollment | It is a severity-of-disease classification system used to assess critically ill patients and predict hospital mortality. The score is calculated based on three main components: Acute Physiology Score (APS) (0-60 points), Age Score (0-6 points) and Chronic Health Condition Score (0-5 points). It has a maximum total score of 71 points. The higher the APACHE II score, the greater the risk of mortality. |
| The Impact of HDIVC on Bedside Index for Severity in Acute Pancreatitis (BISAP) Score | 28 days of enrollment | It is a scoring system used for early assessment of disease severity and prognosis in patients with acute pancreatitis (AP). Each item scores 1 point, total 0-5 points. B - BUN \> 25 mg/dL (Blood Urea Nitrogen \> 25 mg/dL) I - Impaired mental status (Glasgow Coma Scale \[GCS\] \< 15) S - SIRS (Systemic Inflammatory Response Syndrome) (Meeting ≥2 criteria) A - Age \> 60 years P - Pleural effusion BISAP helps predict mortality risk and complications.0-1 points means very low mortality risk (\<1%). 2-3 points means moderate risk (mortality rate \ 2-10%). 4-5 points means high risk (mortality rate \>20%). |
| The Impact of HDIVC on Free Organ Support Duration (FOSD) within 14 Days of Enrollment | 14 days of enrollment | — |
| The Incidence of IPN (Infection-Related Pancreatic Necrosis) | 28 days of enrollment | — |
| ICU Stay Duration | through study completion, an average of 6 months | — |
| Hospitalization Costs | through study completion, an average of 6 months | — |
| Plasma Concentration of Vitamin C Before and After Treatment | 28 days of enrollment | — |
| Adverse events related to Vitamin C | 28 days of enrollment | — |
| The Impact of HDIVC on the Composition of the Gut Microbiota | 28 days of enrollment | The study use the fecal sample to assess the composition of gut microbiota using sequencing techniques (16S rRNA, metagenomics), diversity analysis (alpha and beta diversity), functional profiling (metabolomics) and inflammation markers (calprotectin). |
| The Impact of HDIVC on Pancreatic Necrosis, namely Computed Tomography Severity Index (CTSI). | 28 days of enrollment | It is a scoring system used to assess the severity of acute pancreatitis (AP) based on contrast-enhanced CT (CECT) imaging. CTSI helps predict disease severity, complications, and prognosis. It categorizes acute pancreatitis severity as follows: 0-3 points: Mild pancreatitis, low risk of complications 4-6 points: Moderate pancreatitis, higher risk of complications and organ failure 7-10 points: Severe pancreatitis, high risk of necrosis, organ failure, and mortality |
Countries
China
Outcome results
None listed