Evaluation of Pirfenidone as a Therapy in Patients With Predicted Moderate to Severe Acute Pancreatitis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- percentage of patients having decrease in PAN-PROMISE score by at least 10 points at 72h after initiation of the drug
研究概览
简要总结
The goal of the current pilot clinical trial is to evaluate the safety and tolerability of pirfenidone in patients with predicted moderately severe and severe acute pancreatitis. Pirfenidone is currently approved by FDA for the treatment of idiopathic pulmonary fibrosis. Now, over 5 years of data has accumulated demonstrating safety of its use in humans. The investigators' preclinical data suggest that pirfenidone is very effective in reducing the severity of acute pancreatitis in animal models. Following are the objectives of the proposed clinical trial:
Primary Objective:
- To evaluate the safety and tolerability of pirfenidone, compared to placebo, in patients predicted to have moderately severe or severe AP.
- To evaluate the efficacy of pirfenidone in reducing the laboratory markers of inflammation and improving patient reported outcome measures.
Secondary Objective:
- To evaluate the efficacy of pirfenidone in reducing the severity of acute pancreatitis, as measured by well-defined endpoints.
详细描述
The study is a Randomized Pilot clinical trial evaluating safety and tolerability of pirfenidone in patients with predicted moderately severe to severe acute pancreatitis. There are built in secondary end-points for efficacy. The patients with acute pancreatitis, who present within 48h of establishment of the diagnosis, will be screened for exclusion and inclusion criteria and consented for the clinical trial. Patients with be randomized into placebo or pirfenidone arm and followed daily in-person, while in hospital, and by telephone once discharged from the hospital (weekly for 4 weeks, then monthly for up to 6 months) for study end points.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients 18 - 85 years of age
- •Admitted to hospital for AP, defined by at least 2 of the following 3:
- •amylase or lipase values, or both, that are greater than 3 times the upper limit of normal values
- •characteristic cross-sectional imaging
- •typical upper abdominal pain- acute onset of a persistent, severe, epigastric pain often radiating to the back
- •Patients identified, approached, and consented to administer study medication or placebo within 48 hours of diagnosis of AP.
- •Predicted to have MSAP or SAP by presence of one or more of the following criteria
- •APACHE II ≥ 8
- •Modified Glasgow or Imrie score ≥ 3
- •CRP > 150 mg/dL
- •PASS score > 140 at or within 48 hrs. of admission
- •CT or MRI imaging suggesting pancreatic and/or peri-pancreatic necrosis
排除标准
- •Age < 18 or > 85 years
- •Body weight > 200 kg
- •Presentation to the medical attention > 48 h after diagnosis of AP
- •Inability to recruit, randomize and start the allocated treatment within 48h of start of pain
- •Ongoing AP or diagnosis of AP in previous 30 days
- •Chronic pancreatitis
- •Known hypersensitivity to pirfenidone
- •AST/ALT ≥ 2 times the upper normal limit.
- •Alkaline phosphatase ≥ 2 times the upper normal limit
- •Bilirubin higher than upper normal limit
- •Moderate to severe heart failure and/or coronary heart disease (New York Heart Association (NYHA) Functional Class III/IV)
- •On home oxygen or home mechanical ventilation
- •Advanced liver disease
- •Paralytic ileus or significant nausea and vomiting
- •Chronic Diarrhea
- •Immunosuppressive disorder or on immunosuppressive medications
- •Active or advanced malignancy
- •Known cancer that is end-stage with ongoing palliative care or for which palliative care is appropriate
- •Known established infection prior to the onset of acute pancreatitis
- •Known history of infective hepatitis
- •Known live vaccines or therapeutic infectious agents within one month of admission
- •Known pregnancy or lactation at the time of admission
- •Ongoing photosensitivity and rash
- •Women of childbearing potential who are not on oral or injectable contraceptives or IUDs and do not consent to practice abstinence for period of 4 weeks.
- •Known to be currently participating in a trial testing any investigational medicinal product or participation in a clinical study involving a medicinal product in the last three months
- •Alcohol or substance abuse in the past 2 years
- •Family or personal history of long QT syndrome ( > 500 msec)
- •Medications like fluvoxamine or sildanefil
- •Significant photosensitivity or new rash
- •Renal disease with GFR < 30
- •Any condition other than above that, in the opinion of the investigator, is likely to result in the death of the patient within the next 2 years
- •Any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of pirfenidone
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
Pirfenidone Treatment
干预措施: Pirfenidone Oral Tablet (Drug)
结局指标
主要结局
percentage of patients having decrease in PAN-PROMISE score by at least 10 points at 72h after initiation of the drug
时间窗: 3 days
Measurement of PAN-PROMISE score
Development of anticipated or un-anticipated serious adverse events (class 3 or 4)
时间窗: 6 months
Development of anticipated or un-anticipated serious adverse events (class 3 or 4)
percentage of patients starting and completion of the planned drug treatment
时间窗: 7 days
percentage of patients starting and completion of the planned drug treatment
Changes in C-reactive protein (CRP), TNF-α, interleukin (IL)-6, IL-8 and IL-10 levels
时间窗: 7 days
Compared to base line
次要结局
- cumulative PASS score(duration of admission)
- cumulative PAN-PROMISE score(7)
- Composition outcome(6 months)
- Readmission and/or ER visits(within 30 days and within 6 months)
- PASS score at the time of discharge(duration of admission)
研究者
Nikhil Bush Jayaram
Assistant Professor
University of Alabama at Birmingham