Intravenous Alpha-1 Antitrypsin for Hospitalized Patients With COPD Exacerbations (AECOPD Study)

NCT07125664 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: AECOPD study
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Intravenous augmentation therapy with purified preparations of AAT (Alpha1-antitrypsin) derived from human plasma is a well consolidated specific therapeutic option to treat the severe deficient state of AAT. Prolastin is used to restore the balance between AAT and elastases in the lung and consequently to prevent a further deterioration in the pulmonary emphysema. Recently, in patients with COVID-19, without genetically lowered AAT levels with moderate to severe ARDS, treatment with AAT was demonstrated to be safe, feasible, and biochemically efficacious as an anti-inflammatory therapeutic therapy. The aim of the study, based on biological plausibility, is to evaluate the safety and efficacy (from a biological perspective) of the administration of intravenous plasma-purified AAT as an anti-inflammatory treatment for patients admitted to hospital because of a COPD exacerbation leading to an acute or an acute on chronic respiratory failure. Thirty-six adult patients hospitalized because of a COPD exacerbation leading to an acute or an acute on chronic respiratory failure will be enrolled by the two sites involved in the study, the Pneumology Unit of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) and the Pneumology Unit of IRCCS Istituto Clinico Humanitas, Rozzano (Milano, Italy). Participants will be randomized 2:1 in the active treatment group (standard treatment + IV administration of Prolastin) or in the placebo group (standard treatment+ IV administration of 0.9% sodium chloride). To address the clinical question from a biological perspective, we will investigate the decrease in inflammatory markers in the active treated group in comparison with the placebo group. The primary objective is to demonstrate a significant reduction in systemic inflammation by IV Prolastin administered once at 120 mg per kilogram of body weight in patients with moderate to severe AECOPD, as assessed by the change in plasma concentration of IL6 at 7 days after randomization, in the active treatment group with respect to placebo group. Secondary outcomes are:

1. 1.Difference in change in plasma concentration of IL-1b, IL-5, IL-8, IL-10, and soluble TNF receptor 1 (sTNFR1), CRP at 7 days after randomization.
2. 2.Differences in AAT antielastase activity, the amount of active elastase, the AAT levels in serum at baseline and at 7 days after randomization.
3. 3.Difference in treatment failure rate. Treatment failure is a composite endpoint of need for either NIV or CPAP or need of ETI or need of transfer to ICU or in-hospital death after randomization
4. 4.Impact of AECOPD on overall health, daily life, and perceived well-being in patients with obstructive airways disease by the change of St. George's Respiratory Questionnaire (SGRQ) score from Day 7 to follow-up (30 days after hospital discharge).
5. 5.Differences in type and number of AEs and SAEs in the two groups

Conditions

Acute Exacerbation Chronic Obstructive Pulmonary Disease

Keywords

COPD exacerbations; Intravenous alpha-1 antitrypsin; IL-6; anti-inflammatory

Outcome Measures

Primary Outcomes (1)

• Change in level of circulating IL-6 in plasma

  change in level of circulating IL-6 in plasma at 7 days after IMP administration, as measured by ELISA

  at 7 days after IMP administration

Secondary Outcomes (5)

• Change in plasma concentration of IL-1b, IL-5, IL-8, IL-10, and soluble TNF receptor 1(sTNFR1), CRP

  at 7 days after after randomization

• Differences in the AAT antielastase activity, the amount of active elastase, the AAT levels in serum

  at baseline and at 7 days after randomization

• Treatment failure

  from randomization to 30 days after hospital discharge

• Impact of AECOPD on overall health, daily life, and perceived well-being

  from Day 7 to 30 days after hospital discharge

• Type and number of AEs and SAEs

  from randomization to 30 days after hospital discharged

Study Arms (2)

Prolastin

EXPERIMENTAL

Alpha1-proteinase inhibitor (human), commercially available as Prolastin

Biological: alpha1-proteinase inhibitor, produced from the plasma of human donors (Prolastin 1000 mg, powder and solvent for solution for infusion)

Placebo

PLACEBO COMPARATOR

0.9% sodium chloride solution for infusion ("normal saline")

Drug: Placebo

Interventions

alpha1-proteinase inhibitor, produced from the plasma of human donors (Prolastin 1000 mg, powder and solvent for solution for infusion) BIOLOGICAL

IV Prolastin administered once at 120 mg per kilogram of body weight

Prolastin

Placebo DRUG

\+ IV administration of 0.9% sodium chloride

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed Consent as documented by signature
• Male and female ≥40 years old
• Previous COPD diagnosis with a documented post-bronchodilator FEV1 to FVC ratio (FEV1/FVC) equal to or less than 0.70 or LLN
• Hospitalized for a moderate to severe exacerbation, according to the Rome proposal
• Admission to the respiratory ward by ≤24 hours
• Acute respiratory failure with SpO2 \<92% at room air, or PaO2\< 60 mmHg at room air, or acute on chronic respiratory failure defined as higher Increased oxygen requirements compared with the home standard oxygen prescription
• A positive sputum NEATstik®, that corresponds to an approximate neutrophil elastase concentration of 8 μg·mL-1 (rapid point-of-care test)

You may not qualify if:

• Clinically important pulmonary disease other than COPD (e.g., clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, and primary ciliary dyskinesia)
• Presence of pneumonia or other pleuroparenchymal abnormalities on either chest X-ray or Chest CT scan, performed per routine clinical practice at the hospital admission
• Current diagnosis of asthma according to the GINA, prior history of asthma, or asthma-COPD overlap
• Known AATD as homozygous or composite heterozygous mutation
• Presence of any active malignancy (other than non-melanoma skin cancer)
• Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment that, in the opinion of the Investigator, could:
• Affect the safety of the participant throughout the study
• Influence the findings of the study or their interpretation
• Known diagnosis of selective IgA deficiency defined as a serum IgA of less than 7 mg/dl (0.07 g/L)
• Patient with the immediate need for ETI of NIV (patients already on CPAP or NIV can be included)
• Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product
• Women who are of childbearing potential\*
• Participants that have previously received Prolastin® 1000 mg/40 ml
• Participation in another interventional clinical trials with investigational drugs within the 30 days preceding and during the present study. \* A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the randomisation without an alternative medical cause.

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo

Pavia, Lombardy, 27100, Italy

Location

Related Publications (52)

• Celli BR, Fabbri LM, Aaron SD, Agusti A, Brook R, Criner GJ, Franssen FME, Humbert M, Hurst JR, O'Donnell D, Pantoni L, Papi A, Rodriguez-Roisin R, Sethi S, Torres A, Vogelmeier CF, Wedzicha JA. An Updated Definition and Severity Classification of Chronic Obstructive Pulmonary Disease Exacerbations: The Rome Proposal. Am J Respir Crit Care Med. 2021 Dec 1;204(11):1251-1258. doi: 10.1164/rccm.202108-1819PP. No abstract available.

  PMID: 34570991 BACKGROUND

• Bristow CL. Measuring the Concentration of Active Alpha-1 Antitrypsin in Serum. Methods Mol Biol. 2024;2750:71-77. doi: 10.1007/978-1-0716-3605-3_7.

  PMID: 38108968 BACKGROUND

• Lee MC, Wu WY, Lu HY, Hsieh HN, Wu WH. Conducting the non-inferiority test for the means with unknown coefficient of variation in a three-arm trial. BMC Med Res Methodol. 2023 Aug 11;23(1):183. doi: 10.1186/s12874-023-01990-w.

  PMID: 37568109 BACKGROUND

• Escribano Duenas AM, Martin Garcia M, Tortajada Goitia B, Arenas Villafranca JJ. Case report: Self-administration of alpha-1 antitrypsin therapy: a report of two cases. Front Pharmacol. 2023 Nov 21;14:1291677. doi: 10.3389/fphar.2023.1291677. eCollection 2023.

  PMID: 38074132 BACKGROUND

• Blanco I, Lara B, de Serres F. Efficacy of alpha1-antitrypsin augmentation therapy in conditions other than pulmonary emphysema. Orphanet J Rare Dis. 2011 Apr 12;6:14. doi: 10.1186/1750-1172-6-14.

  PMID: 21486454 BACKGROUND

• Wencker M, Banik N, Buhl R, Seidel R, Konietzko N. Long-term treatment of alpha1-antitrypsin deficiency-related pulmonary emphysema with human alpha1-antitrypsin. Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL)-alpha1-AT-study group. Eur Respir J. 1998 Feb;11(2):428-33. doi: 10.1183/09031936.98.11020428.

  PMID: 9551749 BACKGROUND

• Stoller JK, Fallat R, Schluchter MD, O'Brien RG, Connor JT, Gross N, O'Neil K, Sandhaus R, Crystal RG. Augmentation therapy with alpha1-antitrypsin: patterns of use and adverse events. Chest. 2003 May;123(5):1425-34. doi: 10.1378/chest.123.5.1425.

  PMID: 12740257 BACKGROUND

• Hubbard RC, Sellers S, Czerski D, Stephens L, Crystal RG. Biochemical efficacy and safety of monthly augmentation therapy for alpha 1-antitrypsin deficiency. JAMA. 1988 Sep 2;260(9):1259-64.

  PMID: 3261353 BACKGROUND

• Greulich T, Chlumsky J, Wencker M, Vit O, Fries M, Chung T, Shebl A, Vogelmeier C, Chapman KR, McElvaney NG; RAPID Trial Group. Safety of biweekly alpha1-antitrypsin treatment in the RAPID programme. Eur Respir J. 2018 Nov 29;52(5):1800897. doi: 10.1183/13993003.00897-2018. Print 2018 Nov.

  PMID: 30237305 BACKGROUND

• Murphy MP, McEnery T, McQuillan K, McElvaney OF, McElvaney OJ, Landers S, Coleman O, Bussayajirapong A, Hawkins P, Henry M, Meleady P, Reeves EP, McElvaney NG. alpha1 Antitrypsin therapy modulates the neutrophil membrane proteome and secretome. Eur Respir J. 2020 Apr 30;55(4):1901678. doi: 10.1183/13993003.01678-2019. Print 2020 Apr.

  PMID: 32060059 BACKGROUND

• Bergin DA, Reeves EP, Meleady P, Henry M, McElvaney OJ, Carroll TP, Condron C, Chotirmall SH, Clynes M, O'Neill SJ, McElvaney NG. alpha-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8. J Clin Invest. 2010 Dec;120(12):4236-50. doi: 10.1172/JCI41196. Epub 2010 Nov 8.

  PMID: 21060150 BACKGROUND

• Elliott PR, Pei XY, Dafforn TR, Lomas DA. Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease. Protein Sci. 2000 Jul;9(7):1274-81. doi: 10.1110/ps.9.7.1274.

  PMID: 10933492 BACKGROUND

• Greene CM, McElvaney NG. Proteases and antiproteases in chronic neutrophilic lung disease - relevance to drug discovery. Br J Pharmacol. 2009 Oct;158(4):1048-58. doi: 10.1111/j.1476-5381.2009.00448.x.

  PMID: 19845686 BACKGROUND

• Wewers MD, Casolaro MA, Sellers SE, Swayze SC, McPhaul KM, Wittes JT, Crystal RG. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema. N Engl J Med. 1987 Apr 23;316(17):1055-62. doi: 10.1056/NEJM198704233161704.

  PMID: 3494198 BACKGROUND

• McElvaney NG, Burdon J, Holmes M, Glanville A, Wark PA, Thompson PJ, Hernandez P, Chlumsky J, Teschler H, Ficker JH, Seersholm N, Altraja A, Makitaro R, Chorostowska-Wynimko J, Sanak M, Stoicescu PI, Piitulainen E, Vit O, Wencker M, Tortorici MA, Fries M, Edelman JM, Chapman KR; RAPID Extension Trial Group. Long-term efficacy and safety of alpha1 proteinase inhibitor treatment for emphysema caused by severe alpha1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir Med. 2017 Jan;5(1):51-60. doi: 10.1016/S2213-2600(16)30430-1. Epub 2016 Dec 2.

  PMID: 27916480 BACKGROUND

• Campos MA, Geraghty P, Holt G, Mendes E, Newby PR, Ma S, Luna-Diaz LV, Turino GM, Stockley RA. The Biological Effects of Double-Dose Alpha-1 Antitrypsin Augmentation Therapy. A Pilot Clinical Trial. Am J Respir Crit Care Med. 2019 Aug 1;200(3):318-326. doi: 10.1164/rccm.201901-0010OC.

  PMID: 30965011 BACKGROUND

• McElvaney OJ, McEvoy NL, Boland F, McElvaney OF, Hogan G, Donnelly K, Friel O, Browne E, Fraughen DD, Murphy MP, Clarke J, Choileain ON, O'Connor E, McGuinness R, Boylan M, Kelly A, Hayden JC, Collins AM, Cullen A, Hyland D, Carroll TP, Geoghegan P, Laffey JG, Hennessy M, Martin-Loeches I, McElvaney NG, Curley GF. A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19. Med. 2022 Apr 8;3(4):233-248.e6. doi: 10.1016/j.medj.2022.03.001. Epub 2022 Mar 11.

  PMID: 35291694 BACKGROUND

• Chapman KR, Burdon JG, Piitulainen E, Sandhaus RA, Seersholm N, Stocks JM, Stoel BC, Huang L, Yao Z, Edelman JM, McElvaney NG; RAPID Trial Study Group. Intravenous augmentation treatment and lung density in severe alpha1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Jul 25;386(9991):360-8. doi: 10.1016/S0140-6736(15)60860-1. Epub 2015 May 27.

  PMID: 26026936 BACKGROUND

• Ritzmann F, Chitirala P, Kruger N, Hoffmann M, Zuo W, Lammert F, Smola S, Tov N, Alagem N, Lepper PM, Pohlmann S, Beisswenger C, Herr C, Bals R; AAT-in-COVID-19 Study Group. Therapeutic Application of Alpha-1 Antitrypsin in COVID-19. Am J Respir Crit Care Med. 2021 Jul 15;204(2):224-227. doi: 10.1164/rccm.202104-0833LE. No abstract available.

  PMID: 33961754 BACKGROUND

• McElvaney OJ, O'Connor E, McEvoy NL, Fraughan DD, Clarke J, McElvaney OF, Gunaratnam C, O'Rourke J, Curley GF, McElvaney NG. Alpha-1 antitrypsin for cystic fibrosis complicated by severe cytokinemic COVID-19. J Cyst Fibros. 2021 Jan;20(1):31-35. doi: 10.1016/j.jcf.2020.11.012. Epub 2020 Nov 20.

  PMID: 33288475 BACKGROUND

• Lockett AD, Kimani S, Ddungu G, Wrenger S, Tuder RM, Janciauskiene SM, Petrache I. alpha(1)-Antitrypsin modulates lung endothelial cell inflammatory responses to TNF-alpha. Am J Respir Cell Mol Biol. 2013 Jul;49(1):143-50. doi: 10.1165/rcmb.2012-0515OC.

  PMID: 23526215 BACKGROUND

• Pott GB, Chan ED, Dinarello CA, Shapiro L. Alpha-1-antitrypsin is an endogenous inhibitor of proinflammatory cytokine production in whole blood. J Leukoc Biol. 2009 May;85(5):886-95. doi: 10.1189/jlb.0208145. Epub 2009 Feb 5.

  PMID: 19197072 BACKGROUND

• Nita I, Hollander C, Westin U, Janciauskiene SM. Prolastin, a pharmaceutical preparation of purified human alpha1-antitrypsin, blocks endotoxin-mediated cytokine release. Respir Res. 2005 Jan 31;6(1):12. doi: 10.1186/1465-9921-6-12.

  PMID: 15683545 BACKGROUND

• Janciauskiene S, Wrenger S, Immenschuh S, Olejnicka B, Greulich T, Welte T, Chorostowska-Wynimko J. The Multifaceted Effects of Alpha1-Antitrypsin on Neutrophil Functions. Front Pharmacol. 2018 Apr 17;9:341. doi: 10.3389/fphar.2018.00341. eCollection 2018.

  PMID: 29719508 BACKGROUND

• Aldonyte R, Jansson L, Janciauskiene S. Concentration-dependent effects of native and polymerised alpha1-antitrypsin on primary human monocytes, in vitro. BMC Cell Biol. 2004 Mar 29;5:11. doi: 10.1186/1471-2121-5-11.

  PMID: 15050036 BACKGROUND

• Tilg H, Vannier E, Vachino G, Dinarello CA, Mier JW. Antiinflammatory properties of hepatic acute phase proteins: preferential induction of interleukin 1 (IL-1) receptor antagonist over IL-1 beta synthesis by human peripheral blood mononuclear cells. J Exp Med. 1993 Nov 1;178(5):1629-36. doi: 10.1084/jem.178.5.1629.

  PMID: 7693853 BACKGROUND

• Stockley RA, Bayley DL, Unsal I, Dowson LJ. The effect of augmentation therapy on bronchial inflammation in alpha1-antitrypsin deficiency. Am J Respir Crit Care Med. 2002 Jun 1;165(11):1494-8. doi: 10.1164/rccm.2109013.

  PMID: 12045122 BACKGROUND

• Lewis EC. Expanding the clinical indications for alpha(1)-antitrypsin therapy. Mol Med. 2012 Sep 7;18(1):957-70. doi: 10.2119/molmed.2011.00196.

  PMID: 22634722 BACKGROUND

• McCarthy C, Reeves EP, McElvaney NG. The Role of Neutrophils in Alpha-1 Antitrypsin Deficiency. Ann Am Thorac Soc. 2016 Aug;13 Suppl 4:S297-304. doi: 10.1513/AnnalsATS.201509-634KV.

  PMID: 27564664 BACKGROUND

• Jonigk D, Al-Omari M, Maegel L, Muller M, Izykowski N, Hong J, Hong K, Kim SH, Dorsch M, Mahadeva R, Laenger F, Kreipe H, Braun A, Shahaf G, Lewis EC, Welte T, Dinarello CA, Janciauskiene S. Anti-inflammatory and immunomodulatory properties of alpha1-antitrypsin without inhibition of elastase. Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):15007-12. doi: 10.1073/pnas.1309648110. Epub 2013 Aug 23.

  PMID: 23975926 BACKGROUND

• Janciauskiene SM, Bals R, Koczulla R, Vogelmeier C, Kohnlein T, Welte T. The discovery of alpha1-antitrypsin and its role in health and disease. Respir Med. 2011 Aug;105(8):1129-39. doi: 10.1016/j.rmed.2011.02.002. Epub 2011 Mar 1.

  PMID: 21367592 BACKGROUND

• Ingebrigtsen TS, Marott JL, Rode L, Vestbo J, Lange P, Nordestgaard BG. Fibrinogen and alpha1-antitrypsin in COPD exacerbations. Thorax. 2015 Nov;70(11):1014-21. doi: 10.1136/thoraxjnl-2015-207561. Epub 2015 Aug 24.

  PMID: 26304913 BACKGROUND

• Dahl M, Nordestgaard BG, Lange P, Vestbo J, Tybjaerg-Hansen A. Molecular diagnosis of intermediate and severe alpha(1)-antitrypsin deficiency: MZ individuals with chronic obstructive pulmonary disease may have lower lung function than MM individuals. Clin Chem. 2001 Jan;47(1):56-62.

  PMID: 11148177 BACKGROUND

• Turino GM, Barker AF, Brantly ML, Cohen AB, Connelly RP, Crystal RG, Eden E, Schluchter MD, Stoller JK. Clinical features of individuals with PI*SZ phenotype of alpha 1-antitrypsin deficiency. alpha 1-Antitrypsin Deficiency Registry Study Group. Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1718-25. doi: 10.1164/ajrccm.154.6.8970361.

  PMID: 8970361 BACKGROUND

• Silverman EK, Sandhaus RA. Clinical practice. Alpha1-antitrypsin deficiency. N Engl J Med. 2009 Jun 25;360(26):2749-57. doi: 10.1056/NEJMcp0900449. No abstract available.

  PMID: 19553648 BACKGROUND

• Fregonese L, Stolk J. Hereditary alpha-1-antitrypsin deficiency and its clinical consequences. Orphanet J Rare Dis. 2008 Jun 19;3:16. doi: 10.1186/1750-1172-3-16.

  PMID: 18565211 BACKGROUND

• Bafadhel M, McKenna S, Terry S, Mistry V, Pancholi M, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, Brightling CE. Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2012 Jul 1;186(1):48-55. doi: 10.1164/rccm.201108-1553OC. Epub 2012 Mar 23.

  PMID: 22447964 BACKGROUND

• Waljee AK, Rogers MA, Lin P, Singal AG, Stein JD, Marks RM, Ayanian JZ, Nallamothu BK. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ. 2017 Apr 12;357:j1415. doi: 10.1136/bmj.j1415.

  PMID: 28404617 BACKGROUND

• Sivapalan P, Ingebrigtsen TS, Rasmussen DB, Sorensen R, Rasmussen CM, Jensen CB, Allin KH, Eklof J, Seersholm N, Vestbo J, Jensen JS. COPD exacerbations: the impact of long versus short courses of oral corticosteroids on mortality and pneumonia: nationwide data on 67 000 patients with COPD followed for 12 months. BMJ Open Respir Res. 2019 Mar 30;6(1):e000407. doi: 10.1136/bmjresp-2019-000407. eCollection 2019.

  PMID: 31179005 BACKGROUND

• Aaron SD, Vandemheen KL, Hebert P, Dales R, Stiell IG, Ahuja J, Dickinson G, Brison R, Rowe BH, Dreyer J, Yetisir E, Cass D, Wells G. Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med. 2003 Jun 26;348(26):2618-25. doi: 10.1056/NEJMoa023161.

  PMID: 12826636 BACKGROUND

• Alia I, de la Cal MA, Esteban A, Abella A, Ferrer R, Molina FJ, Torres A, Gordo F, Elizalde JJ, de Pablo R, Huete A, Anzueto A. Efficacy of corticosteroid therapy in patients with an acute exacerbation of chronic obstructive pulmonary disease receiving ventilatory support. Arch Intern Med. 2011 Nov 28;171(21):1939-46. doi: 10.1001/archinternmed.2011.530.

  PMID: 22123804 BACKGROUND

• Thompson WH, Nielson CP, Carvalho P, Charan NB, Crowley JJ. Controlled trial of oral prednisone in outpatients with acute COPD exacerbation. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):407-12. doi: 10.1164/ajrccm.154.2.8756814.

  PMID: 8756814 BACKGROUND

• Niewoehner DE, Erbland ML. Systemic corticosteroids in COPD. An unresolved clinical dilemma. Chest. 1996 Oct;110(4):867-9. doi: 10.1378/chest.110.4.867-a. No abstract available.

  PMID: 8874233 BACKGROUND

• Maltais F, Ostinelli J, Bourbeau J, Tonnel AB, Jacquemet N, Haddon J, Rouleau M, Boukhana M, Martinot JB, Duroux P. Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial. Am J Respir Crit Care Med. 2002 Mar 1;165(5):698-703. doi: 10.1164/ajrccm.165.5.2109093.

  PMID: 11874817 BACKGROUND

• Davies L, Angus RM, Calverley PM. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet. 1999 Aug 7;354(9177):456-60. doi: 10.1016/s0140-6736(98)11326-0.

  PMID: 10465169 BACKGROUND

• Groenke L, Disse B. Blood eosinophil counts as markers of response to inhaled corticosteroids in COPD? Lancet Respir Med. 2015 Aug;3(8):e26. doi: 10.1016/S2213-2600(15)00258-1. No abstract available.

  PMID: 26282478 BACKGROUND

• Baines KJ, Pavord ID, Gibson PG. The role of biomarkers in the management of airways disease. Int J Tuberc Lung Dis. 2014 Nov;18(11):1264-8. doi: 10.5588/ijtld.14.0226.

  PMID: 25299856 BACKGROUND

• Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, McCormick M, Haldar K, Kebadze T, Duvoix A, Lindblad K, Patel H, Rugman P, Dodson P, Jenkins M, Saunders M, Newbold P, Green RH, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, Brightling CE. Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers. Am J Respir Crit Care Med. 2011 Sep 15;184(6):662-71. doi: 10.1164/rccm.201104-0597OC.

  PMID: 21680942 BACKGROUND

• Ingebrigtsen TS, Marott JL, Vestbo J, Hallas J, Nordestgaard BG, Dahl M, Lange P. Characteristics of undertreatment in COPD in the general population. Chest. 2013 Dec;144(6):1811-1818. doi: 10.1378/chest.13-0453.

  PMID: 23989916 BACKGROUND

• Hurst JR, Vestbo J, Anzueto A, Locantore N, Mullerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, Macnee W, Calverley P, Rennard S, Wouters EF, Wedzicha JA; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010 Sep 16;363(12):1128-38. doi: 10.1056/NEJMoa0909883.

  PMID: 20843247 BACKGROUND

• Venkatesan P. GOLD COPD report: 2023 update. Lancet Respir Med. 2023 Jan;11(1):18. doi: 10.1016/S2213-2600(22)00494-5. Epub 2022 Nov 30. No abstract available.

  PMID: 36462509 BACKGROUND

• GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020 Oct 17;396(10258):1204-1222. doi: 10.1016/S0140-6736(20)30925-9.

  PMID: 33069326 BACKGROUND

MeSH Terms

Interventions

alpha 1-Antitrypsin; Powders; Solvents; Solutions

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins; Dosage Forms; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Central Study Contacts

Angelo Guido Corsico, prof

CONTACT

0382501029; a.corsico@smatteo.pv.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: August 8, 2025
• First Posted: August 15, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 7, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 24, 2025

Record last verified: 2025-08

Locations

IT (1)