Standardized Treatment of Pulmonary Exacerbations II

Pulmonary Cystic Fibrosis Clinical Trial

— STOP2  

Official title:

Standardized Treatment of Pulmonary Exacerbations II (STOP2)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02781610
• Other study ID #: STOP2-IP-15
• Status: Completed
• Phase: Phase 4
• Start date: June 2016
• Est. completion date: March 6, 2020

Study information

• Verified date: April 2021
• Source: Seattle Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 982
• Est. completion date: March 6, 2020
• Est. primary completion date: March 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Pulmonary Cystic Fibrosis

Intervention

Drug:
• Standard of care IV antibiotic(s)
IV antibiotics will be selected by the treating physician following standard of care. Duration of treatment is the assigned intervention.

Locations

Country	Name	City	State
Canada	Calgary Canada Adult CF Clinic	Calgary	Alberta
United States	Akron Children's Hospital	Akron	Ohio
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	Augusta University Medical Center	Augusta	Georgia
United States	John Hopkins Hospital	Baltimore	Maryland
United States	Billings Clinic	Billings	Montana
United States	The Children's Hospital Alabama	Birmingham	Alabama
United States	St. Luke's Regional Medical Center	Boise	Idaho
United States	Boston Children's Hospital (BCH)	Boston	Massachusetts
United States	Women and Children's Hospital of Buffalo	Buffalo	New York
United States	The University of Vermont Medical Center Inc.	Burlington	Vermont
United States	North Carolina Children's Hospital	Chapel Hill	North Carolina
United States	Medical University of South Carolina; Medical University of South Carolina Children's Hospital	Charleston	South Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	University Hospital of Cleveland	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Dayton Children's Hospital	Dayton	Ohio
United States	National Jewish Health	Denver	Colorado
United States	Detroit Medical Center; Harper University Hospital	Detroit	Michigan
United States	Shands Hospital	Gainesville	Florida
United States	Hartford Hospital	Hartford	Connecticut
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Joe DiMaggio Children's Hospital (Adult)	Hollywood	Florida
United States	Baylor St. Lukes Medical Center	Houston	Texas
United States	Indiana University Hospital, Indiana University Health	Indianapolis	Indiana
United States	The University of Kansas Hospital	Kansas City	Kansas
United States	UC San Diego Medical Center	La Jolla	California
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	University of Wisconsin Hospital Center	Madison	Wisconsin
United States	University of Miami	Miami	Florida
United States	Froedtert Hospital	Milwaukee	Wisconsin
United States	Ruby Memorial Hospital	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	Robert Wood Johnson University Hospital (New Brunswick, NJ)	New Brunswick	New Jersey
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	The Long Island Jewish Medical Center	New Hyde Park	New York
United States	Beth Israel Medical Center	New York	New York
United States	Columbia University Medical Center	New York	New York
United States	Lucile S. Packard Children's Hospital	Palo Alto	California
United States	Saint Francis Medical Center	Peoria	Illinois
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Medical College of Virginia (Richmond, VA)	Richmond	Virginia
United States	Highland Hospital; Strong Memorial Hospital	Rochester	New York
United States	University of California Davis, Health System	Sacramento	California
United States	Saint Louis University Hospital	Saint Louis	Missouri
United States	St. Louis Washington University Adult - Barnes-Jewish Hospital	Saint Louis	Missouri
United States	University of Washington Medical Center	Seattle	Washington
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	University Medical Center	Tucson	Arizona
United States	University of Texas Health Center at Tyler	Tyler	Texas
United States	New York Medical College	Valhalla	New York
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Health Care (Worcester, MA)	Worcester	Massachusetts

Sponsors (5)

Lead Sponsor	Collaborator
Chris Goss	CF Therapeutics Development Network Coordinating Center, Cystic Fibrosis Foundation, Medical University of South Carolina, University of Washington

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Change in CRISS From Visit 1 to Visit 3 Between ERR-10 Day and ERR-14 Day	Absolute change in respiratory symptoms, as measured by the the Cystic Fibrosis Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CFRSD-CRISS), from baseline/visit 1 (start of IV antibiotic treatment) to last study visit/visit 3 (14 days after the end of IV antibiotic treatment). The Diary asks a participant to state the extent of their 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present 'a great deal' or 'extremely'. A summed score (range from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where the lowest scores indicate improvement of symptoms.	Start of IV antibiotic treatment to14 days after the end of IV antibiotic treatment
Secondary	Change in CRISS From Visit 1 to Visit 3 Between NERR-14 Day and NERR-21 Day	Absolute change in respiratory symptoms, as measured by the the Cystic Fibrosis Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CFRSD-CRISS), from baseline/visit 1 (start of IV antibiotic treatment) to last study visit/visit 3 (14 days after the end of IV antibiotic treatment). The Diary asks a participant to state the extent of their 8 respiratory symptoms: difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present 'a great deal' or 'extremely'. A summed score (range from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where the lowest scores indicate improvement of symptoms.	Start of IV antibiotic treatment to14 days after the end of IV antibiotic treatment
Secondary	Change in Weight From Visit 1 to Visit 3 Between ERR-10 Day and ERR-14 Day	Absolute change in weight (kg) 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	Change in Weight From Visit 1 to Visit 3 Between NERR-14 Day and NERR-21 Day	Absolute change in weight (kg) 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