Clinical trial NCT04885491: A Study to Evaluate the Efficacy, Safety and Tolerability of PDNO Infusion in COVID-19 Patients With Acute Pulmonary Hypertension
Official title: An Open-Label, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of PDNO (Nitrosooxypropanol) Infusion in COVID-19 Patients With Acute Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Pulmonary Hypertension
COVID-19
Keywords: Acute Pulmonary Hypertension
Lead sponsor: Attgeno AB
Sponsor class: INDUSTRY
Collaborators: name: Vinnova
First posted: 2021-05-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Observational period with placebo treatment, followed by treatment with PDNO.
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in MPAP and calculated PVR measured with PAC, at target dose after up-titration and 10 minutes after steady state.
timeFrame: During 24 hours
Secondary outcomes:
measure: Safety and tolerability of PDNO in patients with COVID-19, as measured by incidence of treatment-emergent AEs, SAEs, and AESI.
timeFrame: Through study completion (i.e., Day 30)
measure: 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.
timeFrame: From baseline until Day 7
measure: 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).
timeFrame: At Days 7, 14, 21, and 30.
measure: Time to obtain first negative upper respiratory tract sample in the SARS-CoV-2-rt-PCR assay
timeFrame: From Day 1 to Day 14
measure: Change in troponin I/T and BNP/NT-proBNP
timeFrame: From end of PDNO infusion to Day 7.
measure: Change in the ratio PVR/SVR
timeFrame: During 24 hours
Other outcomes:
measure: Levels of SARS-CoV-2 virus in plasma and sputum/tracheal secretion
timeFrame: From Day 1 to Day 2
measure: Collection of plasma for future analysis of biomarkers such as nitrite and nitrate in plasma (µM)
timeFrame: From Day 1 to Day 7
Locations:
city: Danderyd
country: Sweden
facility: Danderyd Hospital
city: Örebro
country: Sweden
facility: Örebro University Hospital
Study officials:
affiliation: Attgeno AB
name: Cecilia Kemi, PhD
role: STUDY_DIRECTOR
References: