LSALT Peptide vs. Placebo to Prevent ARDS and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19)
- Conditions
- Acute Respiratory Distress SyndromeAcute Kidney InjuryCOVIDSevere Acute Respiratory SyndromeSars-CoV2
- Interventions
- Drug: Placebo
- Registration Number
- NCT04402957
- Lead Sponsor
- Arch Biopartners Inc.
- Brief Summary
To evaluate the proportion of subjects alive and free of respiratory failure (e.g. need for non-invasive or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of the need for continued renal replacement therapy (RRT) on Day 28. The need for continued RRT at Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR on Day 28 \<10 mL/min/1.73 m2.
- Detailed Description
This study is a parallel group, randomized, third-party blinded, multicenter study to assess safety and efficacy of LSALT peptide versus placebo in hospitalized patients with confirmed infection or recent confirmed infection with complications associated with COVID-19. Following screening and after establishing baseline parameters such as lung and renal function, clinical chemistries, coagulation, hematology, and urinalysis, and satisfying all inclusion and exclusion criteria, patients will be randomized to one of two blinded treatment regimens:
1. 100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily
2. 100 mL drug-free IV saline infusion over 2 hours daily.
Thirty (30) patients will be randomized to active drug (LSALT peptide) and 30 patients will be randomized to matching placebo. This study will be third-party blind with only the Pharmacist at the site unblinded for the purpose of preparing drug/placebo for injection.
Patients will be followed for safety and efficacy up to Day 28, with Day 1 being the day of randomization to assess safety. After assessing the risk of ARDS and satisfying all inclusion and exclusion criteria, the patient will be randomized to 5 mg LSALT peptide or blinded placebo to be given intravenously once daily for a maximum of 14 days. Physical and respiratory examinations, vital signs, and adverse events will be recorded throughout the study, including Day 28 (EOS). Blood chemistries, hematology, coagulation, urinalysis, ECG, SARS-CoV-2 tests, eGFR, and chest x-ray (CXR) will be assessed at Day 1 (Screening/Baseline) prior to initiation of study drug, and on Day 3, EOT, and at EOS, as well as when clinically indicated. The ECG at EOS will only be obtained if clinically indicated. An additional CXR will be obtained at time of clinical improvement. Cytokines/biomarkers and pharmacokinetics (PK) will be assessed at Day 1 (Screening/Baseline) prior to initiation of study drug, at 1 (mid-dose) and 2 hours (end of infusion) of drug therapy on Days 1, 3, EOT, and a single blood sample at EOS for cytokines/biomarkers only. Where applicable, a urinary pregnancy test will be obtained at Screening in women of childbearing potential. Questionnaires (APACHE II, SOFA) will be obtained at Baseline, Day 3, EOT, and EOS; venous blood gas (VBG) or HCO3 (bicarbonate) levels may be substituted for arterial blood gas (ABG) if it is considered standard-of-care (SOC) or in the patient's best interest, and results in comparable APACHE II and SOFA scores. Other questionnaires (Berlin Definition and modified Medical Research Council Dyspnea Scale) will be assessed at Baseline, Day 3, EOT, and EOS. IgG, IgA, and IgM antiviral antibodies will be collected at Baseline and EOS. Patients will be maintained on the SOC per institutional guidelines, including prophylaxis or treatment of VTE, throughout the study.
A Data and Safety Monitoring Board (DSMB) will evaluate patients on a continuing basis for primarily safety assessments. Per the DSMB Charter, the DSMB will meet at least monthly if not more frequently based upon enrollment throughout the study period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 61
Not provided
-
Known sensitivity, allergy, or previous exposure to LSALT peptide.
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Exposure to any investigational drug or device <90 days prior to entry into study.
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Treatment with immunomodulators or immunosuppressant drugs, including but not limited to IL-6 inhibitors, TNF inhibitors, anti-IL-1 immunomodulators, and JAK inhibitors within five half-lives or 30 days (whichever is longer) prior to randomization and throughout the study period. However, should any of these treatments become standard-of-care and incorporated into clinical treatment guidelines (e.g. those of WHO or NIH), the treatment is permitted. Further, low-dose oral prednisone (<20 mg/day) and inhaled steroids (e.g. treatment of asthma) are allowed in the study.
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Anticipated transfer to another hospital or medical center within 72 hours, which is not a study site.
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Uncontrolled of poorly treated active hepatitis B (HBV), hepatitis C (HepC), or HIV infection. Those subjects who are positive for HBV, HepC, or HIV but are well-controlled with low viral loads are allowed to participate in this study:
- HBV low viral load defined as <20,000 IU/mL
- HepC low viral load defined as <800,000 IU/mL
- HIV low viral load defined as <5000 copies/mL
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Participation in another drug or device study at any time during this study, for example:
- Ulinastatin 200,000 IU or greater
- High dose intravenous Vitamin C
- Budesonide and formoterol
- Bevacizumab to prevent ARDS
- Dornase alfa to reduce hypoxemia in ventilated trauma patients.
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As indicated in the inclusion criteria, pregnant female patients are excluded from study. Further, female patients who are nursing are excluded from study.
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Has any medical condition considered to be clinically significant and could potentially affect patient safety or study outcome, including but not limited to:
- Acute or chronic kidney disease (stage-4 or -5 renal impairment; eGFR<30 mL/min/1.73 m2 or hemodialysis)
- End-stage malignancy undergoing treatment
- Immunocompromised patients or those with medical/surgical conditions (e.g., solid organ transplantation) which require chronic immunosuppression
- Chronic hematologic disease which, in the opinion of the PI, prohibits the patient from entering into study
- Acute liver injury with AST and/or ALT levels greater than 3x ULN unless recent injury (within 2 weeks) likely due to COVID-19 infection
- History of coagulopathy within the last year as defined by abnormal ACT, aPTT, and/or PT/INR values at least 2-fold outside normal limits, and currently present at screening, and/or
- End-stage lung disease, acute lung injury, severe chronic obstructive pulmonary disease (COPD) as assessed by the GOLD criteria (GOLD Stage IV), or mechanical ventilation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LSALT LSALT peptide 100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily Placebo Placebo 100 mL drug-free IV saline infusion over 2 hours daily
- Primary Outcome Measures
Name Time Method To evaluate the proportion of subjects alive and free of respiratory failure and free of the need for continued renal replacement therapy (RRT) on Day 28 (as per Protocol AB002 - Version 1, dated 09JUNE2020) 28 days Respiratory failure is defined as the need for non-invasive or invasive mechanical ventilation, high flow oxygen \[≥ 6 L/minute\], or ECMO. The need for continued RRT at Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR on Day 28 \<10 mL/min/1.73 m2.
- Secondary Outcome Measures
Name Time Method Vasopressor-free days 28 days Change in hs-troponin levels 28 days Change in baseline modified Medical Research Council (mMRC) score 28 days Change in mMRC score (0 to 4) with 4 being the most severe outcome
Proportion of patients with extrapulmonary organ dysfunction using the daily Sequential Organ Failure Assessment (SOFA) score 28 days Change in SOFA score (0 to 4) with 4 being the most severe outcome
Change in liver function by Alanine Aminotransferase (ALT) test 28 days ALT measured in IU/L
Time to each of mild, moderate, or severe ARDS 28 days Virologic clearance rate 28 days SARS-CoV2 testing by swab (nasopharyngeal, nasal, throat, sputum, or lower respiratory tract) at baseline (Day 1) and every 3 days thereafter until eradication
Change in renal function by estimated Glomerular Filtration Rate (eGFR) test 28 days eGFR measured in ml/min/1.73m2
All-cause mortality 28 days The presence of and severity of ARDS as an ordinal outcome of the proportion of patients who have none, mild, moderate, or severe ARDS 28 days The number of ventilation-free days and ECMO-free days 28 days Length of stay in ICU and hospital (admission to discharge) 28 days Change in activated Partial Thromboplastin Time (aPTT) 28 days aPTT measured in seconds
Time on nasal cannula or oxygen mask 28 days Worst PaO2/FiO2 ratio following enrollment 28 days Change in Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score 28 days Change in APACHE II score (0 to 71) with 71 being the most severe outcome
Change in liver function by Aspartate Transferase (AST) test 28 days AST measured in IU/L
Change in liver function by total bilirubin test 28 days Total bilirubin measured in mg/dL
Change in renal function by serum creatinine (SCr) test 28 days SCr measured in mg/dL
Change in PaO2/FiO2 ratio 28 days Change from maximal radiographic damage to EOT 28 days Change in Activated Coagulation Time (ACT) 28 days ACT measured in seconds
Change in antiviral IgG, IgA, and IgM levels 28 days Immunoglobulins measured in mg/dL
Change in Prothrombin Time (PT)/International Normalized Ratio (INR) 28 days PT measured in seconds
Trial Locations
- Locations (7)
Broward Health Medical Center
🇺🇸Fort Lauderdale, Florida, United States
LSU Health Shreveport
🇺🇸Shreveport, Louisiana, United States
University of Calgary - Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
VA San Diego Healthcare System
🇺🇸San Diego, California, United States
Ankara City Hospital
🇹🇷Ankara, Turkey
Istanbul University Cerrahpasa
🇹🇷Istanbul, Turkey
University of Calgary - Peter Lougheed Centre
🇨🇦Calgary, Alberta, Canada