Clinical trial of Nitric Oxide inhalation therapy in patients with severe PH

JRCT ID: jRCT2051220042

Registered date:09/06/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Pulmonary arterial hypertension (PAH), and Chronic thromboembolic pulmonary hypertension (CTEPH)
• Date of first enrollment: 02/11/2022
• Target sample size: 30
• Study type: Interventional

Intervention(s)

Study drug: Nitric Oxide (INOflo for inhalation 800ppm)
Start inhalation at a concentration of 20 ppm, and if the blood methemoglobin concentration is below 2%, increase the dose by 10 ppm every 5 minutes to a maximum concentration of 40 ppm.
On withdrawal from inhalation, if hemodynamics and oxygenation are stable, reduce inhalation dose by half every 5 minutes, gradually decreasing to 5 ppm. And then, If hemodynamics and oxygenation are stable at 1 ppm, attempt inhalation withdrawal every 5 minutes.

Outcome(s)

• Primary Outcome: Efficacy: Change in Pulmonary vascular resistance (PVR) at 30 minutes after inhalation of study drug

Secondary Outcome

Efficacy:
(1) Catheter findings (total pulmonary vascular resistance (TPR), mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), right atrial pressure (RAP), pulmonary vascular resistance (PVR), systolic pulmonary artery pressure/systolic systolic pressure ratio, ratio of PVR / systemic vascular resistance (SVR), cardiac output (CO), cardiac index (CI), heart rate (HR), mixed venous blood oxygen saturation (SvO2 ), arterial blood oxygen saturation (SaO2 ); change from screening time point to each time point (Day 1, Day 2, Day 3)
(2) Arterial blood partial pressure of oxygen (PaO2) and PaO2/FiO2; change from screening to each time point (Day 1, Day 2, Day 3, Day 7)
(3) Arterial blood to alveolar oxygen partial pressure ratio (AaDO2); change from screening to each time point (Day 1, Day 2, Day 3, and Day 7)
(4) Blood test findings; BNP (change from screening to each time point (Day 1, Day 2, Day 3, Day 7)), lactate (change from screening to each time point (Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8)
(5) Echocardiographic findings (TRPG, IVC diameter); change from screening to each time point (Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7)

Safety:
1) Blood methemoglobin concentration; change from screening to each time point (Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7)
2) Adverse events
3) Systolic and diastolic blood pressure and mean blood pressure; change from screening to each time point (Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8)

Exploratory:
1) SF36; change in each of the 8 items from the screening time point to each time point (Day 3, Day 7, Day 8)
2) Duration of catecholamine use

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Patients who are at least 18 years of age at the time consent is obtained
2) Patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH)
3) Patients who meet all of the following criteria for right heart catheterization
1) Mean pulmonary artery pressure greater than 25 mmHg
2) Pulmonary capillary wedge pressure or left ventricular end-diastolic pressure less than 15 mmHg
3) Pulmonary vascular resistance greater than 3 Wood units
4) WHO-FC III or higher
5) Patients with fluid retention (fluid retention on physical examination or echocardiographic evidence of congestion), low cardiac output (cardiac coefficient less than 2.5 L/min/m2 ), or in need of inotropic drugs
6) Patients with written consent from the patient

Exclude criteria

1) Patients with cardiac disease (Eisenmenger's syndrome) who are completely dependent on a right-left shunt for life support
2) Patients with PAH who are eligible for Calcium channel blockers
3) Patients with pulmonary veno-occlusive disease
4) Patients with pulmonary capillary haemangiomatosis
5) Patients with pulmonary hypertension due to left heart disease
6) Patients with pulmonary hypertension due to pulmonary disease and/or hypoxia
7) Patients with pulmonary hypertension with un clear and/or multifactorial mechanisms
8) Patients with a history of hypersensitivity to the investigational drug
9) Pregnant or lactating women, or patients who cannot consent to contraception during the study
10) Patients who plan to participate in other clinical trials or interventional studies during the period of this study
11) Patients who are judged by the investigator or subinvestigator to be inappropriate to participate in this clinical trial for other reasons.

Related Information

• Primary Sponsor: Ogo Takeshi
• Secondary Sponsor: Mallinckrodt Manufacturing LLC
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development