Safety and Efficacy Study of Acthar in Subjects With ARDS

Phase 2

Withdrawn

• Conditions: Acute Respiratory Distress Syndrome
• Interventions: Drug: H.P. Acthar® Gel (repository corticotropin injection); Drug: Placebo

• Registration Number: NCT02113735
• Lead Sponsor: Mallinckrodt

Brief Summary

This study is being performed to evaluate the potential efficacy and safety of Acthar as a treatment for moderate-severe Acute Respiratory Distress Syndrome (ARDS). Approximately 210 subjects will be randomized to 1 of 6 possible treatment groups in a 3:2:3:2:3:2 ratio. Study medication (SM) will be administered via subcutaneous (SC) injection for 4 weeks using a blinded gradually tapering regimen, and subjects will be followed for 60 days post-randomization.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-04-08
• Study First Submitted QC: 2014-04-14
• Study First Posted: 2014-04-15
• Study Start: 2014-08
• Primary Completion: 2016-08
• Study Completion: 2016-08
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-25
• Last Update Posted: 2017-09-27

Recruitment & Eligibility

• Status: WITHDRAWN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

Inclusion Criteria

1. Patients ≥ 18 years.

2. ARDS as defined by:

   • PaO2 /FiO2 ≤ 200 mmHg with PEEP ≥ 5cm H2O.
   • Bilateral opacities on chest radiography not explained by atelectasis, effusions, nodules, or preexisting disease.
   • Requirement for positive pressure ventilation via an endotracheal tube.
   • Respiratory failure not fully explained by cardiac failure or fluid overload. If no identifiable risk factor for ARDS is identified, left atrial hypertension must be excluded by objective measures (e.g. transthoracic echocardiogram).
   • Criteria 2a, 2b, and 2c must occur within the same 24 hr period.

3. Enrollment between 24 hours and 10 days after ARDS criteria are met.

Exclusion Criteria

1. Subject unwilling to receive or intolerant of SC injections.
2. Subject, surrogate, or physician not committed to full supportive care. A "Do Not Resuscitate" (DNR) order alone without other limitations of care does not require study exclusion.
3. Moribund subject with death perceived to be imminent. For the purposes of this study, moribund is defined by a requirement for ≥ 2 high dose vasopressors AND acute organ failures in ≥ 3 organs for ≥ 24 hours prior to study entry.
4. Home mechanical ventilation (noninvasive ventilation or via tracheotomy) except for continuous positive airway pressure or bi-level positive airway pressure (CPAP/BIPAP) used solely for sleep-disordered breathing prior to onset of ARDS.
5. Known contraindication to Acthar per package insert Section 4 (Appendix C): scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, or adrenal cortical hyperfunction.
6. Gastrointestinal/Hepatic: History of chronic active hepatitis, active Hepatitis B or acute or chronic Hepatitis C infection, OR moderate-severe chronic liver disease as defined by a Child-Pugh Score > 11(http://gihep.com/calculators/hepatology/child-pugh-score/), OR any evidence of hemodynamically significant active gastrointestinal (GI) bleeding.
7. Any subject with signs or symptoms concerning for an active infection that has not been treated for > 48 hours prior to randomization with either empiric broad-spectrum or pathogen-directed anti-microbial therapy.
8. Immune System: Known immune-compromised status, including but not limited to individuals who have undergone organ transplantation or who are known to be positive for the human immunodeficiency virus (HIV).
9. Burns >20% total body surface area, or any burn injury accompanied by smoke inhalational injury.
10. Major surgery within 48 hours before randomization, OR evidence of currently active bleeding postoperatively, OR plan for any major surgery during the study period.
11. Administration of any other investigational drug or participation in an interventional clinical research study for ARDS within 30 days of planned randomization or during the 60 day study duration.
12. Presence of any other clinically significant disease or disorder (including those listed in Appendix C package insert Section 5 [Warnings and Precautions]) which, in the opinion of the Investigator (by its nature or by being inadequately controlled), might put the subject at risk due to participation in the study, or may influence the results of the study or the subject's ability to complete the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1	H.P. Acthar® Gel (repository corticotropin injection)	H.P. Acthar® Gel , 64 U, 0.8 mL daily
Group 2	Placebo	Placebo, 0.8 mL, daily
Group 5	H.P. Acthar® Gel (repository corticotropin injection)	H.P. Acthar® Gel , 16 U, 0.2 mL, 2x daily
Group 6	Placebo	Placebo, 0.2 mL, 2x daily
Group 4	Placebo	Placebo, 0.4 mL, 2x daily
Group 3	H.P. Acthar® Gel (repository corticotropin injection)	H.P. Acthar® Gel , 32 U, 0.4 mL, 2x daily

Primary Outcome Measures

Name	Time	Method
Number of ventilator-free days (subjects alive and breathing without assistance for ≥ 48 hr) by Day 28 after randomization	60 days (28 days of treatment with a 32 day follow-up period)

Secondary Outcome Measures

Name	Time	Method
Mortality at Day 28 and Day 60	60 days (28 days of treatment with a 32 day follow-up period)
Number of ICU-free and hospital free days for all subjects who survive to ICU and hospital discharge, respectively	60 days (28 days of treatment with a 32 day follow-up period)
Number of extra-pulmonary organ failure-free days	60 days (28 days of treatment with a 32 day follow-up period)
Change in PaO2/FiO2 ratio and oxygenation index (OI) from baseline for subjects on mechanical ventilation	60 days (28 days of treatment with a 32 day follow-up period)
Change in Systemic Organ Failure Assessment Score (SOFA) score from baseline.	60 days (28 days of treatment with a 32 day follow-up period)
Number of treatment-emergent serious adverse events	60 days (28 days of treatment with a 32 day follow-up period)
Number, severity and site of new infections developing at least 48 hr after initiation of Study Medication	60 days (28 days of treatment with a 32 day follow-up period)
Proportion of subjects who discontinue treatment because of serious safety concerns	60 days (28 days of treatment with a 32 day follow-up period)