Inhibition of Plasma Kallikrein as a New Therapy for Lung Injury

Phase 1

Active, not recruiting

• Conditions: Lung Injury
• Interventions: Other: Saline control; Drug: Lanadelumab

• Registration Number: NCT04848272
• Lead Sponsor: St Vincent's Institute of Medical Research

Brief Summary

Phase 1 study investigating safety of lanadelumab administration to patients with lung injury

Detailed Description

This study will investigate the safety of inhibition of plasma kallikrein by lanadelumab administration in patients with lung injury.

Study Timeline

• Study First Submitted: 2021-04-13
• Study First Submitted QC: 2021-04-13
• Study First Posted: 2021-04-19
• Study Start: 2021-08-09
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-15
• Last Update Posted: 2024-04-17
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

• Age >18 years admitted to the ICU with primary diagnosis of lung injury. The criteria for the diagnosis of lung injury include five principal elements: hypoxemia (blood oxygen saturation (PaO2) ≤92% when breathing ambient air, ratio of PaO2 to the fraction of inspired oxygen (FiO2) ≤300), diffuse pulmonary infiltrates on chest radiographs, decreased lung compliance, and the absence of congestive heart failure.
• Both males and females will be recruited in the proportion in which they are admitted to the ICU with lung injury.
• Arterial cannula in place as part of usual care for the measurement of blood gases.
• Patients may or may not be intubated and mechanically ventilated.
• Able to provide informed consent, or if unable to do so, a responsible person:

medical treatment decision maker is available (by telephone if necessary) who can be approached to seek consent.

Exclusion Criteria

• Other causes of lung infiltrates: pulmonary oedema, alveolar haemorrhage, adverse drug reactions, radiation injury and the idiopathic pneumonitis syndrome.
• Significant dysfunction of non-pulmonary organs in the opinion of the treating ICU consultant.
• Death is deemed imminent or inevitable or there is underlying disease with a life expectancy of less than 90 days.
• Previously enrolled in this study.
• Enrolled in another study.
• Usually receives home oxygen.
• Usually receives any type of assisted ventilation at home. e.g. continuous positive airway pressure for obstructive sleep apnoea.
• Pregnant or might be pregnant. Women aged 18 to 49 are excluded unless there is documented menopause, hysterectomy or surgical sterilisation, or a pregnancy test is negative.
• Objection from the treating clinician.
• Consent refused by the patient or substitute decision maker.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Saline control	Saline control	Saline control
Lanadelumab 300 mg	Lanadelumab	Lanadelumab 300 mg
Lanadelumab 100 mg	Lanadelumab	Lanadelumab 100 mg
Lanadelumab 30 mg	Lanadelumab	Lanadelumab 30 mg

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Related Adverse Events	28 days	Blood gases, pH, bicarbonate, carbon dioxide and lactic acid levels. If the participant is receiving mechanical ventilation, the ventilator settings will be constantly monitored.; Chest X-ray, as indicated. Constant monitoring of haemodynamics (pulse rate, blood pressure) via an arterial cannula, use of vasoactive medications, and constant monitoring of ECG. Fluid balance, including urine output. Serum creatinine, electrolytes, liver function, creatinine kinase, FBE and coagulation will be measured daily or less frequently as decided by the treating team.; If there is suspicion of infection, then appropriate samples will be taken for microbiological examination.; Neurological function will be assessed several times per day.

Secondary Outcome Measures

Name	Time	Method
Blood bradykinin concentration	0, 6, 12, and 24 hours	Blood bradykinin concentration

Trial Locations

Locations (1)

St Vincent's Hospital Melbourne; 🇦🇺 Melbourne, Victoria, Australia