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

Attgeno

Status and phase: Withdrawn; Phase 2; Phase 1

Conditions: COVID-19; Pulmonary Hypertension

Treatments: Drug: Sodium chloride (placebo); Drug: PDNO

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04885491

2020-PDNO-002

Details and patient eligibility

About

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).

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

Treatment with PDNO

Experimental group

Description:

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.

Treatment:

Drug: PDNO

Drug: Sodium chloride (placebo)