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

Phase 1

Withdrawn

• Conditions: Pulmonary Hypertension; COVID-19
• Interventions: Drug: Sodium chloride (placebo); Drug: PDNO

• Registration Number: NCT04885491
• Lead Sponsor: Attgeno AB

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-15
• Study Start: 2021-05-07
• Study First Submitted QC: 2021-05-12
• Study First Posted: 2021-05-13
• Primary Completion: 2023-04-30
• Study Completion: 2023-04-30
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-31
• Last Update Posted: 2023-08-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment with PDNO	Sodium chloride (placebo)	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 with PDNO	PDNO	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.

Primary Outcome Measures

Name	Time	Method
Change in MPAP and calculated PVR measured with PAC, at target dose after up-titration and 10 minutes after steady state.	During 24 hours	Mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR), as measured with a pulmonary artery catheter (PAC).

Secondary Outcome Measures

Name	Time	Method
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)	* Treatment-emergent adverse events (AEs); * Treatment-emergent serious AEs (SAEs); * Treatment-emergent AEs of special interest (AESI)
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.
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	* Treatment-emergent changes in vital signs (blood pressure, pulse, oxygen saturation, respiratory frequency, body temperature); * Treatment-emergent electrocardiogram (ECG) abnormalities; * Treatment-emergent laboratory abnormalities
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.
Change in the ratio PVR/SVR	During 24 hours	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

Trial Locations

Locations (2)

Örebro University Hospital; 🇸🇪 Örebro, Sweden

Danderyd Hospital; 🇸🇪 Danderyd, Sweden