A Phase 2, Open-label, Clinical Trial of Fluoxetine, a Selective Serotonin Reuptake Inhibitor, in the Treatment of Pulmonary Arterial Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Pulmonary Vascular Resistance (PVR)
研究概览
简要总结
This protocol describes an open-label phase 2 clinical trial of fluoxetine in PAH looking at change in pulmonary vascular resistance (PVR) as the primary endpoint.
In this open-label clinical trial, 18 patients with pulmonary arterial hypertension will be given fluoxetine for 24 weeks. A Right Heart Catheterization will be performed at baseline and 24 weeks. Change in PVR will be the primary endpoint; other hemodynamic endpoints, quality of life, QIDS-SR depression scale, functional class and six-minute walk distance will also be evaluated.
Primary Hypothesis: Fluoxetine treatment for 24 weeks will lead to significantly lower pulmonary vascular resistance in 18 patients with PAH in patients treated in an open-label clinical trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •WHO Group I PAH subtypes of idiopathic PAH and PAH associated with drugs / toxins, connective tissue disease, repaired congenital heart disease and unrepaired atrial septal defect
- •WHO Functional Class II or III
- •Right Heart Catheterization within 3 weeks of study entry with mPAP ≥ 25 mmHg, wedge ≤ 15 mmHg, and PVR ≥ 3 Wood units.
- •Contraception use, (-) urine pregnancy test, not breast feeding (women of childbearing potential)
- •One or more approved PAH therapies for ≥ 3 months, no change in dose for 1 month (endothelin-1 antagonist, phosphodiesterase-5 inhibitor, prostacyclin / prostacyclin analog). Novel approved therapies in one of the three existing classes will also be acceptable as background therapy if they become available during the course of the study; other medication classes are excluded
排除标准
- •WHO Functional Class IV or listed for lung transplant
- •Moderate or greater obstructive lung disease: FEV1/FVC <70% and FEV1 <60%
- •Moderate or greater restrictive lung disease: TLC or FVC <60% (if 50-60%: OK if TLC or FVC ≥50% + PFT stable x1 year + CT with no more than mild lung disease)
- •Other cause for pulmonary hypertension: all other WHO group I diseases (including but not limited to liver disease, HIV), and WHO Groups II-V (i.e. left heart disease, lung disease, chronic PE and miscellaneous causes)
- •High probability VQ or positive CTA
- •Left ventricular ejection fraction <40%
- •Severe liver, renal or other medical or physical disease preventing completion of the study procedures
- •Use of antidepressants within 3 months
研究组 & 干预措施
Fluoxetine
Dosing will be
- Week 1-4: 20 mg daily
- Week 5-8: 40 mg daily
- Week 9-12: 60 mg daily
- Week 13-24: 80 mg daily
干预措施: Fluoxetine (Drug)
结局指标
主要结局
Pulmonary Vascular Resistance (PVR)
时间窗: Baseline and Week 24
Change in PVR between baseline and follow-up will be utilized. PVR is calculated as \[(Pulmonary Artery mean - wedge) / Fick Cardiac Output\]. Fick CO will be used in computing PVR over thermodilution because Fick appears to have greater precision (but not accuracy). The calculation of PVR above is measured in woods unit. Change is derived by getting the difference between baseline and week 24 PVR (Week 24 minus Baseline). mean is then computed by getting the average of the change
次要结局
- 5-HIAA (HYDROXYINDOLE ACETIC ACID) Level(Baseline and Week 24)