Investigator-initiated trial of repeated administration of NK-104-NP in patients with pulmonary hypertension

JRCT ID: jRCT2031180075

Registered date:10/01/2019

Basic Information

• Recruitment status: Suspended
• Health condition(s) or Problem(s) studied: Pulmonary arterial hypertension
• Date of first enrollment: 01/01/2019
• Target sample size: 12
• Study type: Interventional

Intervention(s)

1) NK-104-NP 2 mg, d.i.v. within 1 hour, 4 days
2) NK-104-NP 4 mg, d.i.v. within 1 hour, 4 days
3) NK-104-NP 8 mg, d.i.v. within 1 hour, 4 days

Outcome(s)

• Primary Outcome: Change of pulmonary vascular resistance (PVR) between baseline and day 84

Secondary Outcome

Effectiveness: changes of following values between baseline and Day 84
Mean right atrial pressure (mPAP) at rest
Mean pulmonary arterial pressure (mPAP)
Cardiac output (CO)
Cardiac index (CI)
Pulmonary vascular resistance index (PVRI)
Total pulmonary resistance (TPR)
Mixed venous oxygen saturation (SvO2)
Distance of 6 minutes walk
Modified Borg index
WHO functional class
NT-proBNP concentration
NOx concentration
Total pulmonary resistance index(TPRI)
Systemic vascular resistance index (SVRI)
Pulmonary vascular resistance (PVR)

Safety: Incidences of following events
Adverse effects
Severe adverse effects
Side effect

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 79age old
• Gender: Both

Include criteria

1) Patients with pulmonary hypertension classified as Dana Point group 1 and WHO functional class I to IV.
Idiopathic pulmonary arterial hypertension (IPAH)
Heritable pulmonary arterial hypertension (HPAH)
Drug or toxin-induced pulmonary hypertension
Pulmonary arterial hypertension associated with following diseases
a) Connective tissue diseases
b) Congenial heart diseases (at least 1 year has past after shunt repair at the baseline examinations)
c) HIV infection
2) Patients whose PAH is confirmed by right heart catheterization
Mean pulmonary arterial pressure (mPAP) at rest is over than or equal to 25 mmHg
Pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure is under 15mmHg
3) Patients with over 240 dyn*sec/cm5 PVR at baseline right heart catherization
4) Patients treated with over 2 of 3 types of drugs (prostacyclin analogue, endothelin receptor antagonist, phosphodiesterase-5 inhibitor) and stable over 90 days
5) Over 20 and under 80 years old at the time of consent

Patients with a possibility of pregnancy must confirm their non-pregnant status before administration of NK-104-NP and agree to avoid pregnancy at least 180 days by secure contraception methods. Women with no possibility of pregnancy are defined as women who are post-menopausal state (no menses over 1 year, infertility or post-sterilization state).
6) Patients who have provided written informed consent with their signatures before procedures defined in the protocol.

Exclude criteria

1) Patients with malignancy or undergone surgeries due to malignancy within 5 years.
2) Patients taking statins and can NOT stop them from 3 days before administration of NK-104-NP.
3) Patients taking fibrates and can NOT stop them from 3 days before administration of NK-104-NP.
4) Patients taking cyclosporine.
5) Patients with severe cardiac dysfunction or heart failure (<30% ejection fraction or NYHA class III or over).
6) Patients with untreated severe arrhythmia except symptomatically stable patients with pacemaker or drug therapy.
7) Patients after prosthetic valve replacement (except biomaterials).
8) Patients with acute hepatitis, fulminant hepatitis or progressive liver dysfunction.
9) Patients with moderate or severe liver dysfunction (who can NOT satisfy following criteria) associated with chronic hepatitis etc. except patients with liver cirrhosis.
a) AST/ALT is within 3 times upper limit of shared reference range, b) serum bilirubin is 2 times upper limit of shared reference range.
10) Patients with liver cirrhosis and Child B(moderate) or C(severe) liver dysfunction.
11) Patients with obvious interstitial pneumonia.
12) Patients with biliary atresia.
13) Patients with CK(CPK) elevation over 3 times upper limit of shared reference range.
14) Patients with past-history of hypersensitivity or severe adverse effects by pitavastatin calcium.
15) Patients with severe drug allergy or adverse effects including anaphylactic shock.
16) Patients with alcohol abuse or drug addiction.
17) Patients in other trials at the time of informed consent or patients less than 16 weeks after termination of other test drugs.
18) Patients with pregnancy, patients with a possibility of pregnancy and breast-feeding women.
19) Patients judged to be inappropriate as a candidate of this trial by principal investigator or subinvestigator.

Related Information

• Primary Sponsor: Egashira Kensuke
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development (AMED)
• Secondary ID(s): UMIN000032531