A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment
Authors: Christopher H. Goss, Sonya L. Heltshe, Natalie E. West, Michelle Skalland, Don B. Sanders, Raksha Jain, Tara L. Barto, Barbra Fogarty, Bruce C. Marshall, Donald R. VanDevanter, Patrick A. Flume, Gregory Omlor, Brenda Bourne, Dion Roberts, Vicki Roberts, Samya Nasr, Dawn Kruse, Rachel Linnemann, Tsion Hailemichael, Caralee Forseen, Heidi Stapp, Natalie West, S. Patel, A. Claudio, Jerimiah Lysinger, Amy Harmala, George Solomon, Latona Kersh, Karen Miller, Dixie Durham, Ahmet Uluer, Robert Fowler, Carla Frederick, Nadine Caci, Charlotte Teneback, Julie Sweet, Michael Parkins, Clare Smith, Jennifer Goralski, Kelsey Haywood, Patrick Flume, Caroline Brailsford, Dana Albon, Christie Aderholt, Kimberly McBennett, Cindy Schaefer, Alpa Patel, April Hunt, Raksha Jain, Lauren Schumacher, Hari Polenakovik, Linda Clark, Jerry Nick, Katie Poch, Dana Kissner, James Cahill, Jorge Lascano, Erin Silverman, John McArdle, Alison Champagne, Robert Vender, Lisa Allwein, Lance Cohen, Norma (Jean) Barton, Tara Barto, Ami Patel, Cynthia Brown, Nia Vorhees, Michael Crosser, Lawrence Scott, Alix Ashare, Barbara Rodgers, Robert Zanni, Lisa Koval, Andrew Braun, Sophia Chiron Stevens, Maria Tupayachi Ortiz, Patricia Graham, Julie Biller, Erin Hubertz, Kathryn Moffett, Tammy Clark, Rebecca Griffith, Nancy Martinez, Sabiha Hussain, Fei Chen, Marie Egan, Catalina Guzman, Janice Wang, Aileen Espinal, Patricia Walker, Anne Kukral, Emily DiMango, Sarah Fracasso Francis, Carlos Milla, Colleen Dunn, Subramanyam Chittivelu, Ashley Scott, Daniel Dorgan, Sharon Ng, Joseph Pilewski, Rose Lanzo, Nauman Chaudary, Ryan Hayden, Steven Scofield, Barb Johnson, Brian Morrissey, Brandt Robinson, Douglas Conrad, Jenna Mielke, Moira Aitken, Chami Sanlors, Ravi Nayak, Freda Branch, Daniel Rosenbluth, Molly Siegel, Anil Ghimire, Mary Forell, Cori Daines, Monica Varela, Leslie Couch, Rebekah Hibbard, Allen Dozor, Armando Ramirez, Victor Ortega, Kathryn Kennedy, David Fish, Karen Longtine
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. Objectives: To test differing durations of intravenous antimicrobials for CF exacerbations. Methods: STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7-10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days' total antimicrobial duration; all others were randomized to 14 or 21 days' duration. Measurements and Main Results: The primary outcome was percent predicted FEV1 (ppFEV1) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV1 change was 12.8 and 13.4 for 10 and 14 days, respectively, a ‒0.65 difference (95% CI [‒3.3 to 2.0]), excluding the predefined noninferiority margin. The 21- and 14-day arms experienced 3.3 and 3.4 mean ppFEV1 changes, a difference of ‒0.10 (‒1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive. Conclusions: Among adults with CF with early treatment improvement during exacerbation, ppFEV1 after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days. Clinical trial registered with www.clinicaltrials.gov (NCT02781610).