An Open-Label, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of PDNO (Nitrosooxypropanol) Infusion in COVID-19 Patients With Acute Pulmonary Hypertension
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Attgeno AB
- 试验地点
- 2
- 主要终点
- Change in MPAP and calculated PVR measured with PAC, at target dose after up-titration and 10 minutes after steady state.
研究概览
简要总结
This is an open-label, multicentre study evaluating the effect, safety and tolerability of the two regioisomers 1-(nitrosooxy)propan-2-ol and 2-(nitrosooxy)propan-1-ol (PDNO) infusion given to COVID-19 patients with acute pulmonary hypertension (aPH) and/or acute cor pulmonale (ACP).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to understand and willing to sign an ICF
- •Male and female patients at least 18 years of age
- •Diagnosed with COVID-19 at admission to the ICU
- •Diagnosed with echocardiographic signs of pulmonary artery systolic pressure (PASP) > 40 mmHg
排除标准
- •History of chronic pulmonary hypertension (PH), as judged by the Investigator at screening
- •Known New York Heart Association (NYHA) Functional Class III or IV symptoms
- •Left heart failure with ejection fraction (EF) < 35%
- •Acute coronary syndrome
- •Body Mass Index (BMI) > 45 kg/m^2
- •Estimated glomerular filtration rate (eGFR) < 30 mL/min
- •MetHb > 3%
- •PCO2 > 7
- •Indication of liver disease, defined by serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN) at screening
- •Haemoglobin < 80 g/dL
- •Thrombocytopenia (platelet count < 80000/mm^3)
- •Prothrombin time International ratio (INR) > 1.4
- •Pregnancy, or a positive pregnancy test
- •Ongoing daily treatment the last 3 days with non-steroidal anti-inflammatory drugs
- •Known active malignancy within the past 3 years
- •History of allergy/hypersensitivity to PD or ongoing allergy/hypersensitivity or history of hypersensitivity to drugs with a similar chemical structure or class to PDNO
- •History of any other clinically significant disease or disorder
- •Participation in any interventional clinical study
研究组 & 干预措施
Treatment with PDNO
Placebo treatment administered during the 120-minute observation period, followed by PDNO infusion. PDNO administered as an i.v. infusion of 5-15 minutes, respectively, for the increased planned dose titration steps: 3, 10 and thereafter steps of max 10 nmol/kg/min until the target effect on the mean pulmonary arterial pressure/pulmonary vascular resistance (MPAP/PVR) or a maximal dose of 120 nmol/kg/min is reached.
After 4 patients have been treated, the internal safety review committee (iSRC) will decide if the start dose will be increased. The new start dose could be in the interval 1 to 5 nmol/kg/min.
干预措施: Sodium chloride (placebo) (Drug)
Treatment with PDNO
Placebo treatment administered during the 120-minute observation period, followed by PDNO infusion. PDNO administered as an i.v. infusion of 5-15 minutes, respectively, for the increased planned dose titration steps: 3, 10 and thereafter steps of max 10 nmol/kg/min until the target effect on the mean pulmonary arterial pressure/pulmonary vascular resistance (MPAP/PVR) or a maximal dose of 120 nmol/kg/min is reached.
After 4 patients have been treated, the internal safety review committee (iSRC) will decide if the start dose will be increased. The new start dose could be in the interval 1 to 5 nmol/kg/min.
干预措施: PDNO (Drug)
结局指标
主要结局
Change in MPAP and calculated PVR measured with PAC, at target dose after up-titration and 10 minutes after steady state.
时间窗: During 24 hours
Mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR), as measured with a pulmonary artery catheter (PAC).
次要结局
- Safety and tolerability of PDNO in patients with COVID-19, as measured by incidence of treatment-emergent AEs, SAEs, and AESI.(Through study completion (i.e., Day 30))
- Time to obtain first negative upper respiratory tract sample in the SARS-CoV-2-rt-PCR assay(From Day 1 to Day 14)
- Change in troponin I/T and BNP/NT-proBNP(From end of PDNO infusion to Day 7.)
- Safety and tolerability of PDNO in patients with COVID-19, as measured by incidence of treatment-emergent changes in vital signs, ECG abnormalities, and laboratory abnormalities.(From baseline until Day 7)
- Number of participants with the following clinical outcome (dead, intubated at the intensive care unit [ICU], non-intubated at the ICU, discharged from ICU to other hospital care or discharged to home).(At Days 7, 14, 21, and 30.)
- Change in the ratio PVR/SVR(During 24 hours)