A Study to Evaluate the Efficacy, Safety and Tolerability of PDNO Infusion in COVID-19 Patients With Acute Pulmonary Hypertension

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04885491
• Other study ID #: 2020-PDNO-002
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: May 7, 2021
• Est. completion date: April 30, 2023

Study information

• Verified date: July 2023
• Source: Attgeno AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 30, 2023
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• Sodium chloride (placebo)
Placebo (NaCl, commercially available dilution solution for parenteral use, 9 mg/mL)
• PDNO
PDNO consists of propylene glycol (1,2-propanediol, PD) chemically combined with NO (to be donated). The drug substance is formulated as an inherent mixture of 4 structure analogues. The mixture consists of an equilibrium of the 2 regioisomers 1-(nitrosooxy) propan-2-ol and 2-(nitrosooxy) propan-1-ol. In addition, each regioisomer is a racemic mixture.

Locations

Country	Name	City	State
Sweden	Danderyd Hospital	Danderyd
Sweden	Örebro University Hospital	Örebro

Sponsors (2)

Lead Sponsor	Collaborator
Attgeno AB	Vinnova

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Levels of SARS-CoV-2 virus in plasma and sputum/tracheal secretion		From Day 1 to Day 2
Other	Collection of plasma for future analysis of biomarkers such as nitrite and nitrate in plasma (µM)		From Day 1 to Day 7
Primary	Change in MPAP and calculated PVR measured with PAC, at target dose after up-titration and 10 minutes after steady state.	Mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR), as measured with a pulmonary artery catheter (PAC).	During 24 hours
Secondary	Safety and tolerability of PDNO in patients with COVID-19, as measured by incidence of treatment-emergent AEs, SAEs, and AESI.	Treatment-emergent adverse events (AEs); Treatment-emergent serious AEs (SAEs); Treatment-emergent AEs of special interest (AESI)	Through study completion (i.e., Day 30)
Secondary	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.	Treatment-emergent changes in vital signs (blood pressure, pulse, oxygen saturation, respiratory frequency, body temperature); Treatment-emergent electrocardiogram (ECG) abnormalities; Treatment-emergent laboratory abnormalities	From baseline until Day 7
Secondary	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.
Secondary	Time to obtain first negative upper respiratory tract sample in the SARS-CoV-2-rt-PCR assay		From Day 1 to Day 14
Secondary	Change in troponin I/T and BNP/NT-proBNP		From end of PDNO infusion to Day 7.
Secondary	Change in the ratio PVR/SVR	Pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) will be calculated from the obtained values according to the following formulas: PVR= (mean pulmonary arterial pressure [MPAP] - pulmonary capillary wedge pressure [PCWP])/cardiac output (CO) SVR= (mean arterial pressure [MAP] - central venous pressure [CVP])/CO; Ratio of PVR to SVR = PVR/SVR	During 24 hours