Roflumilast as add-on Therapy in Early Cases of ARDS

Study Overview
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Brief Summary
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Mild cases of ARDS will be included in a two-arm protocol, to receive 500 mcg of roflumilast daily up to 28 days (FDA approved dose for COPD) plus standard of care versus standard of care alone. Approximately 76 hospitalized patients with ARDS will be enrolled in this study. Eligible patients will be randomized at ratio of (1:1) to receive either roflumilast plus standard of care or standard of care alone.

Detailed Description
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• Methodology in details: Informed consent will be obtained from included participants. Mild cases of ARDS will be included in a two-arm protocol, to receive 500 mcg of roflumilast daily up to 28 days (FDA approved dose for COPD) plus standard of care versus standard of care alone. Approximately 76 hospitalized patients with ARDS will be enrolled in this study. Eligible patients will be randomized at ratio of (1:1) to receive either roflumilast plus standard of care or standard of care alone. Randomization: Randomization will be in 1:1 ratio using permuted blocks of different sizes. Random.org website will be used for random selection of a sequence of blocks. The latter will be used to generate a randomized list which will be generated and stored by a third party independent of the study team. For allocation concealment, the list will be used to make sequentially numbered sealed opaque envelopes, each containing the sequential randomization number and allocation of subsequent cases. Envelopes will be handed to the study team member responsible for medication preparation. Each envelope will be opened only after: Screening for eligibility Obtaining consent Recording baseline characters The treatment allocation dictated in the envelope will be documented in the case record form and will be subject to audit to assure correct randomization according to the original list. Intervention: Drug: Roflumilast Roflumilast 500 mcg daily for up to 28 days Total follow up time will be 28 days. Proinflammatory parameters will be assessed at baseline, day 7, day 14, and at the end of treatment. Roflumilast will be combined with standard of care for ARDS. During hospitalization, clinical and laboratory data will be recorded daily in the medical history of the patient and in data collection table of the study. During hospitalization, adverse drug reaction will be monitored clinically and by laboratory tests. In case of an adverse effect or a need to discontinue the treatment, roflumilast should be suspended.

Official Title
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The Potential Anti-inflammatory Effect of Roflumilast as Add-on Therapy in The Management of Hospitalized Patients With Mild Acute Respiratory Distress Syndrome

Conditions
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Respiratory Distress Syndrome, Adult

Intervention / Treatment
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* Drug: Roflumilast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to sign informed consent Patients >18 years old male or female Mild cases of ARDS according to the Berlin criteria (PaO/FiO 200 to 300 mmHg) Exclusion Criteria: Pregnancy and breast feeding History of hypersensitivity to roflumilast Patients with mechanical respiratory assistance (severe ARDS) Patients under treatment with roflumilast for COPD Patients with psychiatric diseases Hepatic cirrhosis (Child-Pugh score B or C) Refused to sign informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Roflumilast add-on<br>Eligible patients will take 500 Mcg of roflumilast once daily (up to 28 days) plus standard of care. | Drug: Roflumilast<br>* Roflumilast 500 mcg daily for up to 28 days Total follow up time will be 28 days. Proinflammatory parameters will be assessed at baseline, day 7, day 14, and at the end of treatment. Roflumilast will be combined with standard of care for ARDS. During hospitalization, clinical and laboratory data will be recorded daily in the medical history of the patient and in data collection table of the study. During hospitalization, adverse drug reaction will be monitored clinically and by laboratory tests. In case of an adverse effect or a need to discontinue the treatment, roflumilast should be suspended.<br>|
| Placebo Comparator: Placebo control<br>Eligible patients will take placebo plus standard of care. | Drug: Placebo<br>* Placebo (identical to roflumilast dosage form) will be used for placebo-comparator group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in clinical picture (two-point reduction in patient's admission status) | Defined as a two-point reduction in patient's admission status on a five-point ordinal scale, or live discharge from hospital whichever came first. • The five-point ordinal scale is as follow: Discharge Hospital admission, not requiring oxygen supplement Hospital admission, requiring oxygen supplement Hospital admission for high flow oxygen therapy or non-invasive mechanical ventilation Hospital admission for mechanical ventilation or extracorporeal membrane oxygenation | Follow up for up to 28 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of change in systemic inflammatory parameters, including ferritin. |  | Weekly assessment (baseline, day7, day14, at the end) for up to 28 days. | 
| Evaluation of change in systemic inflammatory parameters, including CRP. |  | Weekly assessment (baseline, day7, day14, at the end) for up to 28 days. | 
| Evaluation of change in systemic inflammatory parameters, including LDH. |  | Weekly assessment (baseline, day7, day14, at the end) for up to 28 days. | 
| Total hospital stay. |  | Follow up for up to 28 days. |