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

NCT04885491 | Withdrawn Phase 1 DMC

• 1 other identifier: 2020-PDNO-002
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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).

Conditions

Pulmonary Hypertension; COVID-19

Keywords

Acute Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Safety and tolerability of PDNO in patients with COVID-19, as measured by incidence of treatment-emergent AEs, SAEs, and AESI.

  Through study completion (i.e., Day 30)

• 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.

  From baseline until Day 7

• 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.

• Time to obtain first negative upper respiratory tract sample in the SARS-CoV-2-rt-PCR assay

  From Day 1 to Day 14

• Change in troponin I/T and BNP/NT-proBNP

  From end of PDNO infusion to Day 7.

Other Outcomes (2)

• Levels of SARS-CoV-2 virus in plasma and sputum/tracheal secretion

  From Day 1 to Day 2

• Collection of plasma for future analysis of biomarkers such as nitrite and nitrate in plasma (µM)

  From Day 1 to Day 7

Study Arms (1)

Treatment with PDNO

EXPERIMENTAL

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.

Drug: Sodium chloride (placebo); Drug: PDNO

Interventions

Sodium chloride (placebo) DRUG

Placebo (NaCl, commercially available dilution solution for parenteral use, 9 mg/mL)

Also known as: NaCl

Treatment with PDNO

PDNO DRUG

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.

Also known as: Nitrosooxypropanol

Treatment with PDNO

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Attgeno AB: lead
• Vinnova: collaborator

Study Sites (2)

Danderyd Hospital

Danderyd, 182 88, Sweden

Location

Örebro University Hospital

Örebro, 701 85, Sweden

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; COVID-19

Interventions

Sodium Chloride; 1-(nitrosooxy)propan-2-ol and 2-(nitrosooxy)propan-1-ol drug combination

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Cecilia Kemi, PhD

  Attgeno AB

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Observational period with placebo treatment, followed by treatment with PDNO.

Study Record Dates

• First Submitted: February 15, 2021
• First Posted: May 13, 2021
• Study Start: May 7, 2021
• Primary Completion: April 30, 2023
• Study Completion: April 30, 2023
• Last Updated: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2)