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Pulmonary HypertensionPhase 1/2NCT04885491

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

A Phase 1/2 study testing PDNO in people with Pulmonary Hypertension and COVID-19, run by Attgeno AB at 2 sites in Sweden.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pulmonary Hypertension, COVID-19
What is being tested?
PDNO
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
2 sitesSweden
Study dates
7 May 2021to 30 Apr 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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 locations and contacts

2 sites in 1 country.

Sweden2 sites

  • Danderyd Hospital

    Danderyd, 182 88

  • Örebro University Hospital

    Örebro, 701 85

Other trials in Sweden

About this study

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

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).

Being tested
Sodium chloride (placebo), PDNO
Keywords
Acute Pulmonary Hypertension
Medical subject headings
Hypertension, Pulmonary, COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sodium chloride (placebo)Drug

    Also called NaCl

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

  • PDNODrug

    Also called Nitrosooxypropanol

    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.

Study groups in NCT04885491
Study groupRoleWhat they receive
Treatment with PDNOExperimentalPlacebo 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.
Receives: Drug: Sodium chloride (placebo); Drug: PDNO

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: During 24 hours

Secondary outcomes (6)

  1. 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)

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

  2. 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

    Measured: From baseline until Day 7

  3. 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).

    Measured: At Days 7, 14, 21, and 30.

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

    Measured: From Day 1 to Day 14

  5. Change in troponin I/T and BNP/NT-proBNP

    Measured: From end of PDNO infusion to Day 7.

  6. 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

    Measured: During 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2021
  2. Study start7 May 2021
  3. Primary completion30 Apr 2023
  4. Study completion30 Apr 2023

Why it stopped: Since the availability of vaccines, a drastic drop in number of patients with increased PAP was observed and when the WHO re-categorized the COVID-19 pandemic from PHEIC to an "established and ongoing health issue" the study was withdrawn.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Observational period with placebo treatment, followed by treatment with PDNO.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04885491
Sponsor's protocol ID
2020-PDNO-002
Status last verified
Jul 2023
First submitted
15 Feb 2021
Last updated
1 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PDNO in people with Pulmonary Hypertension and COVID-19, run by Attgeno AB at 2 sites in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 1 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in MPAP and calculated PVR measured with PAC, at target dose after up-titration and 10 minutes after steady state. (time frame: During 24 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04885491.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2023.

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