Standardized Treatment of Pulmonary Exacerbations II

NCT02781610 | Completed Phase 4 Results DMC

• 1 other identifier: STOP2-IP-15
• Study Type: interventional
• Target: 982
• Locations: 2 countries
• Sites: 58

Brief Summary

Cystic fibrosis (CF), a life-shortening genetic disease, is marked by acute episodes during which symptoms of lung infection increase and lung function decreases. These pulmonary exacerbations are treated with varying antibiotics for varying time periods based on needs determined by individual patients, their families, and the health care providers. Cystic fibrosis pulmonary guidelines for the treatment of pulmonary exacerbation published by the Cystic Fibrosis Foundation (CFF) in 2009 provided recommendations for treatment and also identified key questions for which additional studies were needed. A strong desire among clinicians to reduce treatment durations (and reduce cost, inconvenience, and potential toxicities) is in conflict with belief that patients not responding robustly to treatment might benefit from extending treatment. This randomized, controlled, open-label study is designed to evaluate the efficacy and safety of differing durations of IV treatment, given in the hospital or at home for a pulmonary exacerbation in adult patients with CF.

Conditions

Pulmonary Cystic Fibrosis

Keywords

Cystic fibrosis; Pulmonary exacerbation; Antibiotic; Treatment duration; Lung infection; Cystic Fibrosis Foundation; Cystic Fibrosis Foundation National Patient Registry

Outcome Measures

Primary Outcomes (2)

• Absolute Change in FEV1 % Predicted From Visit 1 to Visit 3 Between ERR-10 Day and ERR-14 Day

  Absolute change in FEV1 % predicted from baseline/visit 1 (start of IV antibiotic treatment) to last study visit/visit 3 (14 days after the end of IV antibiotic treatment).

  Start of IV antibiotic treatment to 14 days after the end of IV antibiotic treatment

• Absolute Change in FEV1 % Predicted From Visit 1 to Visit 3 Between NERR-14 Day and NERR-21

  Absolute change in FEV1 % predicted from baseline/visit 1 (start of IV antibiotic treatment) to last study visit/visit 3 (14 days after the end of IV antibiotic treatment).

  Start of IV antibiotic treatment to14 days after the end of IV antibiotic treatment

Secondary Outcomes (4)

• Change in CRISS From Visit 1 to Visit 3 Between ERR-10 Day and ERR-14 Day

  Start of IV antibiotic treatment to14 days after the end of IV antibiotic treatment

• Change in CRISS From Visit 1 to Visit 3 Between NERR-14 Day and NERR-21 Day

  Start of IV antibiotic treatment to14 days after the end of IV antibiotic treatment

• Change in Weight From Visit 1 to Visit 3 Between ERR-10 Day and ERR-14 Day

  Start of IV antibiotic treatment to14 days after the end of IV antibiotic treatment

• Change in Weight From Visit 1 to Visit 3 Between NERR-14 Day and NERR-21 Day

  Start of IV antibiotic treatment to14 days after the end of IV antibiotic treatment

Study Arms (4)

ERR-10

OTHER

ERR treatment duration - 10 Day Standard of care IV antibiotic(s) will be selected by the treating physician. Duration of treatment is the assigned intervention.

Drug: Standard of care IV antibiotic(s)

ERR-14

OTHER

ERR treatment duration - 14 Day Standard of care IV antibiotic(s) will be selected by the treating physician. Duration of treatment is the assigned intervention.

Drug: Standard of care IV antibiotic(s)

NERR-14

OTHER

NERR treatment duration - 14 Day Standard of care IV antibiotic(s) will be selected by the treating physician. Duration of treatment is the assigned intervention.

Drug: Standard of care IV antibiotic(s)

NERR-21

OTHER

NERR treatment duration - 21 Day Standard of care IV antibiotic(s) will be selected by the treating physician. Duration of treatment is the assigned intervention.

Drug: Standard of care IV antibiotic(s)

Interventions

Standard of care IV antibiotic(s) DRUG

IV antibiotics will be selected by the treating physician following standard of care. Duration of treatment is the assigned intervention.

ERR-10; ERR-14; NERR-14; NERR-21

Eligibility Criteria

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

You may qualify if:

• Male or female ≥18 years of age at Visit 1
• Documentation of a CF diagnosis
• Enrolled in the Cystic Fibrosis Foundation National Patient Registry (CFFNPR) prior to Visit 1 (US sites only)
• At the time of Visit 1, there is a plan to initiate IV antibiotics for a pulmonary exacerbation
• Performed spirometry at Visit 1 and Visit 2 and willing to perform spirometry at Visit 3
• Completed the CRISS questionnaire at Visit 1 and Visit 2 and willing to complete the Cystic Fibrosis Respiratory Symptoms Diary (CFRSD) questionnaire at Visit 3
• Willing to adhere to a specific treatment duration determined by initial response to treatment and subsequent randomization
• Willing to return for follow up Visit 3
• Written informed consent obtained from the subject or subject's legal representative

You may not qualify if:

• Previous randomization in this study
• Treatment with IV antibiotics in the 6 weeks prior to Visit 1
• Admission to the intensive care unit for current pulmonary exacerbation in the two weeks prior to Visit 2, unless admission was due to a desensitization protocol
• Pneumothorax in the two weeks prior to Visit 2
• Primary diagnosis for current hospitalization is unrelated to worsening lower respiratory symptoms (e.g., pulmonary clean out, distal intestinal obstruction syndrome (DIOS), sinusitis)
• Massive hemoptysis defined as \> 250 cc in a 24 hour period or 100 cc/day over 4 consecutive days occurring in the two weeks prior to Visit 2
• Current pulmonary exacerbation thought to be due to allergic bronchopulmonary aspergillosis (ABPA)
• At Visit 1, receiving ongoing treatment with a duration of more than 2 weeks with prednisone equivalent to \>10mg/day
• History of solid organ transplantation
• Receiving antimicrobial therapy to treat non-tuberculous mycobacterium (e.g., M. abscessus, M. avium complex) in the two weeks prior to Visit 2

Sponsors & Collaborators

• Chris Goss: lead
• Cystic Fibrosis Foundation: collaborator
• CF Therapeutics Development Network Coordinating Center: collaborator
• Medical University of South Carolina: collaborator
• University of Washington: collaborator

Study Sites (58)

The Children's Hospital Alabama

Birmingham, Alabama, 35233, United States

Location

Providence Alaska Medical Center

Anchorage, Alaska, 99519-6604, United States

Location

University Medical Center

Tucson, Arizona, 85724, United States

Location

UC San Diego Medical Center

La Jolla, California, 92037, United States

Location

Lucile S. Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

University of California Davis, Health System

Sacramento, California, 95817, United States

Location

National Jewish Health

Denver, Colorado, 80206, United States

Location

Hartford Hospital

Hartford, Connecticut, 06106, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

Shands Hospital

Gainesville, Florida, 32610, United States

Location

Joe DiMaggio Children's Hospital (Adult)

Hollywood, Florida, 33021, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Augusta University Medical Center

Augusta, Georgia, 30912, United States

Location

St. Luke's Regional Medical Center

Boise, Idaho, 83712, United States

Location

Saint Francis Medical Center

Peoria, Illinois, 61603, United States

Location

Indiana University Hospital, Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

The University of Kansas Hospital

Kansas City, Kansas, 66160, United States

Location

John Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Boston Children's Hospital (BCH)

Boston, Massachusetts, 02115, United States

Location

University of Massachusetts Memorial Health Care (Worcester, MA)

Worcester, Massachusetts, 01655, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109-5212, United States

Location

Detroit Medical Center; Harper University Hospital

Detroit, Michigan, 48201, United States

Location

Saint Louis University Hospital

St Louis, Missouri, 63110, United States

Location

St. Louis Washington University Adult - Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Billings Clinic

Billings, Montana, 59107-7000, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Monmouth Medical Center

Long Branch, New Jersey, 07740, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Robert Wood Johnson University Hospital (New Brunswick, NJ)

New Brunswick, New Jersey, 08903, United States

Location

Women and Children's Hospital of Buffalo

Buffalo, New York, 14222, United States

Location

The Long Island Jewish Medical Center

New Hyde Park, New York, 11040, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Highland Hospital; Strong Memorial Hospital

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

North Carolina Children's Hospital

Chapel Hill, North Carolina, 27517, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

University Hospital of Cleveland

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina; Medical University of South Carolina Children's Hospital

Charleston, South Carolina, 29425, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Baylor St. Lukes Medical Center

Houston, Texas, 77030, United States

Location

University of Texas Health Center at Tyler

Tyler, Texas, 75708-3154, United States

Location

The University of Vermont Medical Center Inc.

Burlington, Vermont, 05401, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Medical College of Virginia (Richmond, VA)

Richmond, Virginia, 23298, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Ruby Memorial Hospital

Morgantown, West Virginia, 26506, United States

Location

University of Wisconsin Hospital Center

Madison, Wisconsin, 53792, United States

Location

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Calgary Canada Adult CF Clinic

Calgary, Alberta, T2N 4N1, Canada

Location

Related Publications (6)

• McElvaney OJ, Heltshe SL, Odem-Davis K, West NE, Sanders DB, Fogarty B, VanDevanter DR, Flume PA, Goss CH. Adjunctive Systemic Corticosteroids for Pulmonary Exacerbations of Cystic Fibrosis. Ann Am Thorac Soc. 2024 May;21(5):716-726. doi: 10.1513/AnnalsATS.202308-673OC.

  PMID: 38096105 DERIVED

• Thornton CS, Caverly LJ, Kalikin LM, Carmody LA, McClellan S, LeBar W, Sanders DB, West NE, Goss CH, Flume PA, Heltshe SL, VanDevanter DR, LiPuma JJ. Prevalence and Clinical Impact of Respiratory Viral Infections from the STOP2 Study of Cystic Fibrosis Pulmonary Exacerbations. Ann Am Thorac Soc. 2024 Apr;21(4):595-603. doi: 10.1513/AnnalsATS.202306-576OC.

  PMID: 37963297 DERIVED

• Gold LS, Hansen RN, Patrick DL, Tabah A, Heltshe SL, Flume PA, Goss CH, West NE, Sanders DB, VanDevanter DR, Kessler L. Health care costs in a randomized trial of antimicrobial duration among cystic fibrosis patients with pulmonary exacerbations. J Cyst Fibros. 2022 Jul;21(4):594-599. doi: 10.1016/j.jcf.2022.03.001. Epub 2022 Mar 14.

  PMID: 35300932 DERIVED

• VanDevanter DR, Heltshe SL, Skalland M, West NE, Sanders DB, Goss CH, Flume PA. C-reactive protein (CRP) as a biomarker of pulmonary exacerbation presentation and treatment response. J Cyst Fibros. 2022 Jul;21(4):588-593. doi: 10.1016/j.jcf.2021.12.003. Epub 2021 Dec 18.

  PMID: 34933824 DERIVED

• Goss CH, Heltshe SL, West NE, Skalland M, Sanders DB, Jain R, Barto TL, Fogarty B, Marshall BC, VanDevanter DR, Flume PA; STOP2 Investigators. A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment. Am J Respir Crit Care Med. 2021 Dec 1;204(11):1295-1305. doi: 10.1164/rccm.202102-0461OC.

  PMID: 34469706 DERIVED

• Holland P, Jahnke N. Single versus combination intravenous anti-pseudomonal antibiotic therapy for people with cystic fibrosis. Cochrane Database Syst Rev. 2021 Jun 23;6(6):CD002007. doi: 10.1002/14651858.CD002007.pub5.

  PMID: 34159577 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Limitations and Caveats

Analysis was not done on the combined total of all four treatment duration arms. Interpreting the total column within demographics is inappropriate for this study design.

Results Point of Contact

• Title: Michelle Skalland (Biostatistician)
• Organization: Seattle Children's

michelle.skalland@seattlechildrens.org

206-884-7519

Study Officials

• Chris Goss, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

• Patrick Flume, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine and Pediatrics

Study Record Dates

• First Submitted: May 12, 2016
• First Posted: May 24, 2016
• Study Start: June 1, 2016
• Primary Completion: March 6, 2020
• Study Completion: March 6, 2020
• Last Updated: May 19, 2021
• Results First Posted: April 8, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (57); CA (1)