Prophylactic Topical Epinephrine to Reduce Transbronchial Lung Biopsy-related Hemorrhage in Lung Transplant Recipients: a Prospective Double-blind Placebo-controlled Trial (PROPHylactic Epinephrine in Transbronchial Biopsy [PROPHET] Trial)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 2
- 主要终点
- Intra-procedural Hemorrhage Grading by the Performing Bronchoscopist
研究概览
简要总结
Bleeding poses potential for significant complication after transbronchial lung biopsies. The investigators hypothesize that prophylactic intrabronchial instillation of topical epinephrine will reduce the likelihood of bleeding. The investigators plan a double-blind, placebo controlled trial to evaluate this hypothesis.
详细描述
The role of prophylactic topical epinephrine in improving hemostasis and prevention of clinically-significant pulmonary hemorrhage has never been studied formally in the past, despite its common use by pulmonologists performing bronchoscopic TBLB. Lung transplant recipients undergo multiple bronchoscopies and TBLBs for surveillance and evaluation of ACR as well as lung infection, especially during the first year post-transplantation. This population may have a predilection to TBLB-related bleeding and may benefit from measures to reduce the frequency and magnitude of this relatively common complication.
In the PROPHET trial, the investigators intend to assess the degree of biopsy-related bleeding, measures taken to control bleeding, and potential effects of bleeding on completion of the intended procedure in 50 bronchoscopy procedures performed on single and double lung transplant recipients, randomized to prophylactic topical epinephrine versus placebo (normal saline). The study participant, physician performing the TBLB, and independent observer reviewing the procedure recording will all be blinded to the randomization. Further use of measures to control bleeding that occurs during the procedure as well as the decision to complete the procedure as planned or to abort it prematurely will be left to the discretion of the performer. In this way, the investigators aim to elucidate a potential role of topical epinephrine in the prevention of TBLB-related airway bleeding in lung transplant recipients and assess whether the dose and volume of instillation used in the investigators' institution comprises an effective means to prevent hemorrhagic complications of TBLB.
HYPOTHESIS
The investigators hypothesize that prophylactic instillation of topical epinephrine prior to performance of TBLB will decrease the frequency and extent of biopsy-related hemorrhage as well as result in fewer procedures being aborted earlier than intended due to bleeding complications as well as shorter overall procedure time due to the preventive effect on bleeding. Concomitantly, the investigators hypothesize that the instillation of topical epinephrine will not be associated with a serious adverse event profile in comparison to placebo.
SPECIFIC AIMS
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects, ≥18 years of age.
- •Single- or double-lung transplant recipients scheduled for bronchoscopy with TBLB.
- •Willingness to sign an informed consent for study participation.
排除标准
- •Age <18 years.
- •Pregnancy.
- •Inability to understand and provide a written informed consent.
- •Exclusion criteria for TBLB:
- •Platelet count <50 K/microL.
- •International normalized ratio (INR) >1.
- •Known bleeding diathesis.
- •Use of prophylactic or therapeutic dose of unfractionated heparin within 6 hours of the procedure.
- •Use of prophylactic dose of low molecular weight heparin within 12 hours of the procedure.
- •Use of therapeutic dose of low molecular weight heparin within 24 hours of the procedure.
- •Use of oral direct thrombin inhibitors or oral factor 10a inhibitors within 48 hours of the procedure.
- •Use of clopidogrel, ticlopidine, ticagrelor, or prasugrel within 5 days of the procedure.
- •Uremia, defined as estimated glomerular filtration rate (eGFR) ≤30 mL/min.
- •Moderate to severe pulmonary hypertension as defined by a mean pulmonary artery pressure of >40 mm Hg on right heart catheterization or an estimated pulmonary artery systolic pressure of >62 mm Hg on transthoracic echocardiography, both performed within 1 year of the procedure.
- •An additional synchronous procedure with possible bleeding (bronchoalveolar lavage and endobronchial biopsy allowed).
- •Decompensated liver cirrhosis, defined as the presence of clinically significant ascites, clinical evidence of esophageal or gastric varices, or history of bleeding from gastric or esophageal varices.
- •Prior history of TBLB-related airway bleeding requiring admission to the hospital or advanced measures to achieve hemostasis, including endotracheal intubation, bronchial blocker application, bronchial artery embolization, or surgical intervention.
- •Exclusion criteria for application of topical epinephrine:
- •Systolic heart failure with an ejection fraction (EF) of <35% as assess by echocardiography performed within one year prior to the procedure.
- •Myocardial infarction, acute coronary syndrome, percutaneous coronary intervention, or coronary artery bypass surgery within 6 months prior to the procedure.
- •Symptoms and/or ECG findings suggestive of ongoing cardiac ischemia on the day of the procedure.
- •Moderate- to severe-grade cardiac valvulopathy as assessed by echocardiography performed within one year prior to the procedure.
- •Inadequately controlled supraventricular arrhythmia, including atrial fibrillation, atrial flutter, and atrio-ventricular node re-entrant tachycardia (AVNRT) as revealed by ECG or cardiac monitoring at the time of the procedure.
- •Presence of an internal cardioverter/defibrillator.
- •History of second or third degree (complete) heart block or sick sinus syndrome.
- •Baseline ECG or cardiac monitoring revealing frequent occurrence (≥10 events per minute) of atrial or ventricular ectopy documented prior to or at the time of the procedure.
- •History of ventricular arrhythmias requiring pharmacologic or electrical cardioversion within the 2 years preceding the procedure.
- •Serum potassium of <3.0 mmol/L within the week prior to the procedure.
- •Serum glucose level of ≥300 mg/dL within the week prior to the procedure.
- •Any history of critical ischemia related to peripheral arterial disease.
- •Persistent resting heart rate (HR) measurement of ≥120 beats per minute prior to or at the time of the procedure.
- •Persistent resting systolic blood pressure (SBP) measurement of ≥180 mm Hg prior to or at the time of the procedure.
- •Persistent resting diastolic blood pressure (DBP) measurement of ≥110 mm Hg prior to or at the time of the procedure.
- •History of acute closed-angle glaucoma within one year of the procedure.
- •Diagnosis of pheochromocytoma requiring pharmacologic therapy with an alpha adrenoreceptor blocker at the time of the procedure.
- •Diagnosis of thyrotoxicosis requiring pharmacologic therapy with an anti-thyroid agent at the time of the procedure.
研究组 & 干预措施
Prophylactic topical epinephrine
Study participants who meet inclusion and exclusion criteria and allocated to this arm will be randomized to receive prophylactic endobronchial topical epinephrine in a blinded manner prior to performance of transbronchial lung biopsy.
干预措施: Topical epinephrine (Drug)
Placebo
Study participants who meet inclusion and exclusion criteria and allocated to this arm will be randomized to receive prophylactic endobronchial topical placebo in the form of normal saline in a blinded manner prior to performance of transbronchial lung biopsy.
干预措施: Placebos (Drug)
结局指标
主要结局
Intra-procedural Hemorrhage Grading by the Performing Bronchoscopist
时间窗: This outcome will be analyzed at the time of procedure performance and up to 48 hours following the procedure.
Intra-procedural hemorrhage will be graded by the performing bronchoscopist according to the following scale: 1. No hemorrhage. 2. Mild hemorrhage - Any bleeding originating from the biopsy target airway requiring wedging of the bronchoscope or "in and out" motion in order to achieve hemostasis. 3. Moderate hemorrhage - Any bleeding originating from the biopsy target airway requiring in addition to maneuvering the bronchoscope application of iced saline or topical epinephrine or placing the patient with the bleeding lung in the dependent position. 4. Severe hemorrhage - Any bleeding originating from the biopsy target airway requiring, in addition to the above-mentioned maneuvers, early termination of the procedure or necessitating application of balloon tamponade, endotracheal intubation, application of a bronchial blocker, or use of other invasive measures to achieve hemostasis, such as bronchial artery embolization or surgical intervention.
次要结局
未报告次要终点
研究者
Robert M Reed
Professor of Medicine
University of Maryland, Baltimore