Clinical trial NCT02781610: Standardized Treatment of Pulmonary Exacerbations II
Official title: Standardized Treatment of Pulmonary Exacerbations II (STOP2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Cystic Fibrosis
Keywords: Cystic fibrosis
Pulmonary exacerbation
Antibiotic
Treatment duration
Lung infection
Cystic Fibrosis Foundation
Cystic Fibrosis Foundation National Patient Registry
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: Cystic Fibrosis Foundation
name: CF Therapeutics Development Network Coordinating Center
name: Medical University of South Carolina
name: University of Washington
First posted: 2016-05-24
Enrollment: 982
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The study will assess the non-inferiority of 10 days versus 14 days treatment duration among patients who have an early robust improvement (ERR subjects) and the superiority of 21 days versus 14 days treatment duration among the subjects who do not meet the definition of ERR (non-ERR; NERR).

Subjects will undergo pulmonary function testing (spirometry) and complete a respiratory symptom score \[Chronic Respiratory Infection Symptom Score (CRISS)\] at initiation of IV treatment (Baseline/ Visit 1) and at Day 7-10 (Visit 2). At Visit 2, subjects will be allocated to groups ERR or NERR based on their initial clinical response as determined by the change in forced expiratory volume in 1 second (FEV1; percent of predicted) and CRISS from Baseline and then randomized to an IV treatment duration (nested within group).

ERR subjects \[≥8% predicted improvement in FEV1 from Visit 1 to Visit 2 and CRISS reduction of ≥11 points from Visit 1 to Visit 2\] will be randomized 1:1 to either 10 days or 14 days total IV antibiotic treatment duration. Remaining (NERR) subjects will be randomized 1:1 to receive either 14 or 21 days total IV antibiotic treatment duration. All subjects will be evaluated again at Visit 3, 14 days following scheduled completion of IV antibiotic treatment.

Eligibility criteria: Inclusion Criteria:

Key Inclusion Criteria:

* 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

Exclusion Criteria:

Key Exclusion Criteria

* 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

Primary outcomes:
measure: Absolute Change in FEV1 % Predicted From Visit 1 to Visit 3 Between ERR-10 Day and ERR-14 Day
timeFrame: Start of IV antibiotic treatment to 14 days after the end of IV antibiotic treatment
measure: Absolute Change in FEV1 % Predicted From Visit 1 to Visit 3 Between NERR-14 Day and NERR-21
timeFrame: Start of IV antibiotic treatment to14 days after the end of IV antibiotic treatment
Secondary outcomes:
measure: Change in CRISS From Visit 1 to Visit 3 Between ERR-10 Day and ERR-14 Day
timeFrame: Start of IV antibiotic treatment to14 days after the end of IV antibiotic treatment
measure: Change in CRISS From Visit 1 to Visit 3 Between NERR-14 Day and NERR-21 Day
timeFrame: Start of IV antibiotic treatment to14 days after the end of IV antibiotic treatment
measure: Change in Weight From Visit 1 to Visit 3 Between ERR-10 Day and ERR-14 Day
timeFrame: Start of IV antibiotic treatment to14 days after the end of IV antibiotic treatment
measure: Change in Weight From Visit 1 to Visit 3 Between NERR-14 Day and NERR-21 Day
timeFrame: Start of IV antibiotic treatment to14 days after the end of IV antibiotic treatment
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The Children's Hospital Alabama
state: Alabama
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Tucson
country: United States
facility: University Medical Center
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Medical Center
state: California
city: Palo Alto
country: United States
facility: Lucile S. Packard Children's Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis, Health System
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Gainesville
country: United States
facility: Shands Hospital
state: Florida
city: Hollywood
country: United States
facility: Joe DiMaggio Children's Hospital (Adult)
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Boise
country: United States
facility: St. Luke's Regional Medical Center
state: Idaho
city: Peoria
country: United States
facility: Saint Francis Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Hospital, Indiana University Health
state: Indiana
city: Kansas City
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: Baltimore
country: United States
facility: John Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital (BCH)
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Health Care (Worcester, MA)
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Detroit
country: United States
facility: Detroit Medical Center; Harper University Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Saint Louis University Hospital
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Washington University Adult - Barnes-Jewish Hospital
state: Missouri
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital (New Brunswick, NJ)
state: New Jersey
city: Buffalo
country: United States
facility: Women and Children's Hospital of Buffalo
state: New York
city: New Hyde Park
country: United States
facility: The Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: Highland Hospital; Strong Memorial Hospital
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Chapel Hill
country: United States
facility: North Carolina Children's Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: University Hospital of Cleveland
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina; Medical University of South Carolina Children's Hospital
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: Baylor St. Lukes Medical Center
state: Texas
city: Tyler
country: United States
facility: University of Texas Health Center at Tyler
state: Texas
city: Burlington
country: United States
facility: The University of Vermont Medical Center Inc.
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Richmond
country: United States
facility: Medical College of Virginia (Richmond, VA)
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Morgantown
country: United States
facility: Ruby Memorial Hospital
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospital Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert Hospital
state: Wisconsin
city: Calgary
country: Canada
facility: Calgary Canada Adult CF Clinic
state: Alberta
Study officials:
affiliation: University of Washington
name: Chris Goss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Patrick Flume, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.