Steroid therapy in patients with acute severe pancreatitis for resolution of organ failure: A randomized, controlled, double blinded trial
试验速览
- 阶段
- 2/3 期
- 状态
- 尚未招募
- 入组人数
- 202
- 试验地点
- 5
- 主要终点
- Time of resolution of organ failure within 28 days from randomization. Resolution will be defined as Modified Marshall score of one or less.
研究概览
简要总结
Rationale: Severe acute pancreatitis (SAP) is associated with organ failure, and the 28-day mortality may be as high as 25-30%. Dysregulated immune response and systemic inflammation are implicated in its pathogenesis. Currently, there is no approved therapy to control systemic hyperinflammation, and the management is largely supportive.
Novelty: Steroid therapy has the potential for controlling dysregulated immune response with a reduction of systemic inflammation in SAP. Experimental studies, including our own, have shown improvement in organ failure with steroid therapy in the SAP animal model. A Phase 2 pilot study of steroid therapy for SAP in humans has demonstrated improvement in organ failure without untoward adverse events.
Objective: To compare the time for resolution of organ failure with steroid therapy compared to placebo in patients with SAP and ongoing organ failure.
Methods: It will be a multicenter, randomized, double-blind, placebo-controlled trial. Patients with SAP and ongoing organ failure (Marshall score of 2 or more) will be included in the study. They will be randomized to receive either intravenous methyl prednisolone 64 mg or an identical-looking placebo in addition to standard of care and will be tapered over 10 days depending upon the clinical response. Time to resolution of the organ failure will be the primary outcome. Adverse events, 30-day mortality, resolution of cytokine storm syndrome, hospital stay, and development of infected pancreatic necrosis will be secondary outcomes.
Expected Outcome: Steroid therapy might emerge as a treatment option for SAP and ongoing organ failure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 12.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Diagnosis of Acute Pancreatitis as per revised Atlanta Classification.
- •Patients presenting within seven days of onset of pain.
- •Presence of any organ failure (Modified Marshal grade greater than or equal to 2) i.e. cardiovascular, respiratory or renal and APACHE II score greater than or equal to 8 or systemic inflammatory response syndrome greater than 24 hours (SIRS should be assessed at two time points greater than 6 hours apart) or BISAP score greater than 3.
排除标准
- •Patients with Chronic Pancreatitis
- •Pregnancy and breast feeding
- •Age less than 12 years or greater than 75 years
- •Major comorbidity such as decompensated cirrhosis, Advanced heart failure (stage D), significant lung parenchymal or airway disease with NYHA grade greater than or equal to 3, advanced chronic kidney disease (stage greater than or equal to 4), untreated HIV infection, untreated cancer.
- •Patient already on immune-suppressive therapy
- •Major psychiatry disorders such as psychosis, schizophrenia, major depression, bipolar disorder etc.
- •Uncontrolled diabetes (HbA1C greater than 8), uncontrolled hypertension (systolic blood pressure greater than or equal to 140 mm Hg and diastolic blood pressure greater than or equal to 90 mm Hg as per eighth joint national committee criteria)
- •Brain dead patient or patients with two organ failure (each grade
- •Acute cholecystitis
- •Active tuberculosis
- •Known adrenal insufficiency
- •Acute gastrointestinal bleed within last 7 days
- •Presence of disseminated intravascular coagulation (DIC)
- •Encephalopathy as defined by Glassgow Coma scale less than or equal to 9.
结局指标
主要结局
Time of resolution of organ failure within 28 days from randomization. Resolution will be defined as Modified Marshall score of one or less.
时间窗: 4 weeks
次要结局
- Organ Failure resolution(28 days)
- All Cause mortality(4 weeks)
- Resolution of cytokine storm syndrome(4 weeks)
- Need for mechanical ventilation or hemodialysis(4 weeks)
- Duration of ICU stay(4 weeks)
- Development of infected necrosis(3 months)
- Need for drainage of collection(3 months)
- Need for necrosectomy(3 months)
- Adverse events(28 days)
研究者
Soumya Jagannath Mahapatra
All India Institute of Medical Sciences, new Delhi