Roflumilast as add-on Therapy in Early Cases of ARDS

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

• 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.

Study Overview

• Status: Completed
• Conditions: Respiratory Distress Syndrome, Adult
• Intervention / Treatment: Drug: Roflumilast; Drug: Placebo

Detailed Description

• 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:

1. Screening for eligibility
2. Obtaining consent

3. 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

1. Roflumilast 500 mcg daily for up to 28 days
2. Total follow up time will be 28 days.
3. Proinflammatory parameters will be assessed at baseline, day 7, day 14, and at the end of treatment.
4. Roflumilast will be combined with standard of care for ARDS.
5. 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.
6. During hospitalization, adverse drug reaction will be monitored clinically and by laboratory tests.
7. In case of an adverse effect or a need to discontinue the treatment, roflumilast should be suspended.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Cairo University Hospitals
  • Doki
    • Giza, Doki, Egypt
      • Misr International Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Roflumilast add-on; Eligible patients will take 500 Mcg of roflumilast once daily (up to 28 days) plus standard of care.	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.
PLACEBO_COMPARATOR: Placebo control; Eligible patients will take placebo plus standard of care.	Drug: Placebo; Placebo (identical to roflumilast dosage form) will be used for placebo-comparator group.

What is the study measuring?

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	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.

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Principal Investigator: Eman A Abdel Rasheed, Professor, Cairo University

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 21, 2021
• Primary Completion (ACTUAL): December 30, 2021
• Study Completion (ACTUAL): January 1, 2022

Study Registration Dates

• First Submitted: January 16, 2021
• First Submitted That Met QC Criteria: February 5, 2021
• First Posted (ACTUAL): February 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): April 4, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: MS-292-2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No