Effects of Roflumilast in Hospitalized Chronic Obstructive Pulmonary Disease( COPD) on Mortality and Re-hospitalization

NCT01973998 | Completed Phase 3 Results

• 1 other identifier: 21474
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Background: COPD exacerbations add considerably to patients' burden because they: (1) cause frequent hospital admissions and relapses or readmissions, (2) contribute directly to the death of many patients, either during hospitalization or shortly thereafter, (3) cause patients significant stress, prolonged physical discomfort, disability and dramatically reduced quality of life, (4) consume the majority of the resources available to manage this chronic condition, (5) frequently progress to a severe stage warranting hospitalization before any abortive treatment is instituted, and (6) may hasten the progressive loss of lung function, a steady decline that is a cardinal feature of COPD itself. Hence, investigations of new therapies to treat COPD patients who are hospitalized with a severe exacerbation are desperately needed. Objective: To test the feasibility of roflumilast to decrease all cause readmission and mortality 180 days after hospitalization for acute COPD exacerbation. Methods: Parallel-group, prospective, randomized, double blind, placebo-controlled trial of roflumilast 500 ug daily vs. placebo in approximately 100 hospitalized AECOPD patients. Inclusion Criteria. Primary diagnosis of AECOPD; admission to the hospital \<12 hours; patient age \>40, \< 80 years old; cigarette smoking \> 10 pack-years. Exclusion Criteria. Prior diagnosis or high suspicion for asthma; pulmonary edema, pneumonia, interstitial lung disease or significant bronchiectasis; intubated and mechanically ventilated at the time of evaluation; active liver disease, or transaminase elevations (\> 3xULN); history of heavy ethanol use; history of suicidal behavior ≤ 2 years or suicidal ideation ≤ 6 months prior to enrollment; pregnant or lactating females. Those on the following excluded medications: P450 inducers and CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously

Conditions

COPD

Keywords

COPD; Emphysema; Roflumilast; readmission

Outcome Measures

Primary Outcomes (1)

• Time to All-cause Mortality or Re-hospitalization During the 180 Days Post-randomization.

  A combined endpoint of time to all-cause mortality or re-hospitalization during the 180 days post-randomization was used.

  180 days

Secondary Outcomes (1)

• Respiratory Death or Respiratory Re-hospitalization

  180 days

Other Outcomes (1)

• Assess Tolerance of Roflumilast vs. Placebo in Hospitalized AECOPD

  180 days

Study Arms (2)

Roflumilast

EXPERIMENTAL

500 ug tablet daily for 180 days

Drug: Roflumilast

Placebo

PLACEBO COMPARATOR

Placebo 1 tablet daily x 180 days

Drug: Placebo

Interventions

Roflumilast DRUG

PDE4 inhibitor

Also known as: Daliresp

Roflumilast

Placebo DRUG

Inactive substance.

Also known as: Inactive substance

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary diagnosis of AECOPD defined as acute increase in dyspnea, sputum volume, and/or sputum purulence without other identified cause; admission to the hospital \<12 hours; patient age \>40, \< 80 years old; cigarette smoking \> 10 pack-years; informed written consent.

You may not qualify if:

• Prior diagnosis or high suspicion for asthma based on investigator judgment; pulmonary edema, pneumonia, interstitial lung disease or significant bronchiectasis based on admission chest x-ray; intubated and mechanically ventilated at the time of evaluation; active liver disease, or transaminase elevations (\> 3xULN); history of alcoholism or heavy ethanol use; history of suicidal behavior ≤ 2 years or suicidal ideation ≤ 6 months prior to enrollment; pregnant or lactating females. Those on the following excluded medications: P450 inducers (e.g., rifampicin, phenobarbital, carbamazepine, and phenytoin) and CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously (e.g., erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine.

Sponsors & Collaborators

• Temple University: lead
• Forest Laboratories: collaborator

Study Sites (1)

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Emphysema

Interventions

Roflumilast

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Small sample size, short duration of exposure (6 months), single center nature, absence of chronic bronchitic symptoms in all subjects and lack of mortality events as a measurable endpoint.

Results Point of Contact

• Title: Michael R. Jacobs - Director of Research Development
• Organization: Lewis Katz School of Medicine Temple University

michael.jacobs@tuhs.temple.edu

2157072242

Study Officials

• Gerard J Criner, MD

  Temple University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Pulmonary and Critical Care Medicine

Study Record Dates

• First Submitted: October 27, 2013
• First Posted: November 1, 2013
• Study Start: November 1, 2013
• Primary Completion: November 10, 2017
• Study Completion: November 30, 2017
• Last Updated: March 12, 2020
• Results First Posted: March 12, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal as determined by the investigators at Temple University.

Locations

US (1)