A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis
Summary: Background: In trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | EClinicalMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537022004199 |
| _version_ | 1811240824142299136 |
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| author | John A. Tayek Andrew A. Stolz Danh V. Nguyen M. Wayne Fleischman John A. Donovan Joseph M. Alcorn Daniel C-K. Chao Aliya Asghar Timothy R. Morgan Divya Birudaraju Greg Botwin Hema Buddha Lavanya Cherukuri Sheena Cruz Monique French Rachel Gonzalez Jessica Gozum Rebecca Gutierrez Sajad Hamal Preston Head Carol Jones Neil Kaplowitz Robert Lee Lauren MacHarg Susan Milstein Yuxin Ouyang Christy Rico Cory Zarick |
| author_facet | John A. Tayek Andrew A. Stolz Danh V. Nguyen M. Wayne Fleischman John A. Donovan Joseph M. Alcorn Daniel C-K. Chao Aliya Asghar Timothy R. Morgan Divya Birudaraju Greg Botwin Hema Buddha Lavanya Cherukuri Sheena Cruz Monique French Rachel Gonzalez Jessica Gozum Rebecca Gutierrez Sajad Hamal Preston Head Carol Jones Neil Kaplowitz Robert Lee Lauren MacHarg Susan Milstein Yuxin Ouyang Christy Rico Cory Zarick |
| author_sort | John A. Tayek |
| collection | DOAJ |
| description | Summary: Background: In trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States. Methods: This prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score ≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg subcutaneously) on Day 1 and Day 8 (clinicaltrials.gov NCT02776059). SOC was 28 days of either pentoxifylline or prednisolone, as determined by the patient's primary physician. The second injection of pegfilgrastim was not administered if the white blood cell count exceeded 30,000/mm3 on Day 8. Primary outcome was survival at Day 90. Secondary outcomes included the incidence of acute kidney injury (AKI), hepatorenal syndrome (HRS), hepatic encephalopathy, or infections. Findings: The study was terminated early due to COVID19 pandemic. Eighteen patients were randomized to SOC and 16 to SOC+pegfilgrastim. All patients received prednisolone as SOC. Nine patients failed to receive a second dose of pegfilgrastin due to WBC > 30,000/mm3 on Day 8. Survival at 90 days was similar in both groups (SOC: 0.83 [95% confidence interval [CI]: 0.57–0.94] vs. pegfilgrastim: 0.73 [95% CI: 0.44–0.89]; p > 0.05; CI for difference: -0.18–0.38). The incidences of AKI, HRS, hepatic encephalopathy, and infections were similar in both treatment arms and there were no serious adverse events attributed to pegfilgrastim. Interpretation: This phase II trial found no survival benefit at 90 days among subjects with AH who received pegfilgrastim+prednisolone compared with subjects receiving prednisolone alone. Funding: was provided by the United States National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism U01-AA021886 and U01-AA021884. |
| first_indexed | 2024-04-12T13:26:52Z |
| format | Article |
| id | doaj.art-21ce9efa24d34c9a9784997ac1ab32fa |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-04-12T13:26:52Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-21ce9efa24d34c9a9784997ac1ab32fa2022-12-22T03:31:17ZengElsevierEClinicalMedicine2589-53702022-12-0154101689A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitisJohn A. Tayek0Andrew A. Stolz1Danh V. Nguyen2M. Wayne Fleischman3John A. Donovan4Joseph M. Alcorn5Daniel C-K. Chao6Aliya Asghar7Timothy R. Morgan8Divya BirudarajuGreg BotwinHema BuddhaLavanya CherukuriSheena CruzMonique FrenchRachel GonzalezJessica GozumRebecca GutierrezSajad HamalPreston HeadCarol JonesNeil KaplowitzRobert LeeLauren MacHargSusan MilsteinYuxin OuyangChristy RicoCory ZarickDepartment of Medicine, Harbor-UCLA Medical Center and Lundquist Institute, Torrance, CA, United StatesLAC-USC Medical Center, Los Angeles, CA and the Hepatology Section, Division of Medicine, University of Southern California, Los Angeles, CA, United StatesDivision of General Internal Medicine, Department of Medicine, University of California, Irvine, CA, United StatesDepartment of Medicine, Harbor-UCLA Medical Center and Lundquist Institute, Torrance, CA, United StatesLAC-USC Medical Center, Los Angeles, CA and the Hepatology Section, Division of Medicine, University of Southern California, Los Angeles, CA, United StatesDivision of Gastroenterology, Department of Medicine University of New Mexico, Albuquerque, New Mexico and Medical Service, Raymond G. Murphy VA Medical Center, Albuquerque, NM, United StatesGastroenterology Section, Medical Service, VA Healthcare System, Loma Linda, CA, United StatesResearch Service, VA Healthcare System, Long Beach, CA, United StatesGastroenterology Section, Medical Service, VA Healthcare System, Long Beach, CA, United States; Division of Gastroenterology, Department of Medicine, University of California, Irvine, CA, United States; Corresponding author at: VA Long Beach Healthcare System-11 (GI), 5901 E. Seventh Street, Long Beach, CA 90822, United States.Summary: Background: In trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States. Methods: This prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score ≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg subcutaneously) on Day 1 and Day 8 (clinicaltrials.gov NCT02776059). SOC was 28 days of either pentoxifylline or prednisolone, as determined by the patient's primary physician. The second injection of pegfilgrastim was not administered if the white blood cell count exceeded 30,000/mm3 on Day 8. Primary outcome was survival at Day 90. Secondary outcomes included the incidence of acute kidney injury (AKI), hepatorenal syndrome (HRS), hepatic encephalopathy, or infections. Findings: The study was terminated early due to COVID19 pandemic. Eighteen patients were randomized to SOC and 16 to SOC+pegfilgrastim. All patients received prednisolone as SOC. Nine patients failed to receive a second dose of pegfilgrastin due to WBC > 30,000/mm3 on Day 8. Survival at 90 days was similar in both groups (SOC: 0.83 [95% confidence interval [CI]: 0.57–0.94] vs. pegfilgrastim: 0.73 [95% CI: 0.44–0.89]; p > 0.05; CI for difference: -0.18–0.38). The incidences of AKI, HRS, hepatic encephalopathy, and infections were similar in both treatment arms and there were no serious adverse events attributed to pegfilgrastim. Interpretation: This phase II trial found no survival benefit at 90 days among subjects with AH who received pegfilgrastim+prednisolone compared with subjects receiving prednisolone alone. Funding: was provided by the United States National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism U01-AA021886 and U01-AA021884.http://www.sciencedirect.com/science/article/pii/S2589537022004199Alcoholic hepatitisPegfilgrastimPhase IIRandomized clinical trial |
| spellingShingle | John A. Tayek Andrew A. Stolz Danh V. Nguyen M. Wayne Fleischman John A. Donovan Joseph M. Alcorn Daniel C-K. Chao Aliya Asghar Timothy R. Morgan Divya Birudaraju Greg Botwin Hema Buddha Lavanya Cherukuri Sheena Cruz Monique French Rachel Gonzalez Jessica Gozum Rebecca Gutierrez Sajad Hamal Preston Head Carol Jones Neil Kaplowitz Robert Lee Lauren MacHarg Susan Milstein Yuxin Ouyang Christy Rico Cory Zarick A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis EClinicalMedicine Alcoholic hepatitis Pegfilgrastim Phase II Randomized clinical trial |
| title | A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis |
| title_full | A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis |
| title_fullStr | A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis |
| title_full_unstemmed | A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis |
| title_short | A phase II, multicenter, open-label, randomized trial of pegfilgrastim for patients with alcohol-associated hepatitis |
| title_sort | phase ii multicenter open label randomized trial of pegfilgrastim for patients with alcohol associated hepatitis |
| topic | Alcoholic hepatitis Pegfilgrastim Phase II Randomized clinical trial |
| url | http://www.sciencedirect.com/science/article/pii/S2589537022004199 |
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