CAL02, a novel antitoxin liposomal agent, in severe pneumococcal pneumonia: a first-in-human, double-blind, placebo-controlled, randomised trial

The Lancet Infectious Diseases

Volumn 19, Issue 6, 2019, Pages 620-630

  Laterre, Pierre François ^a   Colin, Gwenhael ^b   Dequin, Pierre François ^c   Dugernier, Thierry ^d   Boulain, Thierry ^e   Azeredo da Silveira, Samareh ^f   Lajaunias, Frédéric ^f   Perez, Antonio ^f   François, Bruno ^g,h  

^a CLINIQUES UNIVERSITAIRES SAINT LUC   (Belgium)

^b Medical Surgical Intensive Care Unit District Hospital Center   (France)

^c UNIVERSITY HOSPITAL OF TOURS   (France)

^d Clinique Saint Pierre of Ottignies   (Belgium)

^e CENTRE HOSPITALIER RÉGIONAL D ORLÉANS   (France)

^f Medical Department   (Switzerland)

^g LIMOGES UNIVERSITY HOSPITAL   (France)

^h UMR 1092   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; ANTITOXIN; C REACTIVE PROTEIN; CAL 02; LIPOSOME; PHOSPHORUS; PLACEBO; PROCALCITONIN; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; ANTIINFECTIVE AGENT;

ADULT; ANEMIA; ANTIBIOTIC SENSITIVITY; ANTIBIOTIC THERAPY; APACHE; ARTICLE; ATRIAL FIBRILLATION; BELGIUM; BLOOD CULTURE; CHOLESTASIS; CLINICAL ARTICLE; COMMUNITY ACQUIRED PNEUMONIA; CONSTIPATION; CONTROLLED STUDY; DISEASE DURATION; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; ESCHERICHIA COLI; FEMALE; FIRST IN HUMAN STUDY; FRANCE; HUMAN; HYPERGLYCEMIA; HYPERNATREMIA; HYPOGLYCEMIA; HYPOKALEMIA; HYPONATREMIA; HYPOTENSION; KIDNEY FAILURE; KLEBSIELLA PNEUMONIAE; LIVER CELL DAMAGE; LOW DRUG DOSE; MALE; METHICILLIN SUSCEPTIBLE STAPHYLOCOCCUS AUREUS; MIDDLE AGED; MULTICENTER STUDY; PHOSPHATE BLOOD LEVEL; PLEURA EFFUSION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SEQUENTIAL ORGAN FAILURE ASSESSMENT SCORE; SIDE EFFECT; STREPTOCOCCUS PNEUMONIA; THROMBOCYTOPENIA; TRIACYLGLYCEROL LEVEL; ADOLESCENT; AGED; CLINICAL TRIAL; COMMUNITY ACQUIRED INFECTION; DOUBLE BLIND PROCEDURE; RANDOMIZED CONTROLLED TRIAL (TOPIC); TREATMENT OUTCOME; VERY ELDERLY; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ANTI-BACTERIAL AGENTS; ANTITOXINS; BELGIUM; COMMUNITY-ACQUIRED INFECTIONS; DOUBLE-BLIND METHOD; FEMALE; FRANCE; HUMANS; LIPOSOMES; MALE; MIDDLE AGED; PNEUMONIA, PNEUMOCOCCAL; RANDOMIZED CONTROLLED TRIALS AS TOPIC; TREATMENT OUTCOME; YOUNG ADULT;

EID: 85065880481     PISSN: 14733099     EISSN: 14744457     Source Type: Journal    
DOI: 10.1016/S1473-3099(18)30805-3     Document Type: Article

References (28)

1. Los, FC, Randis, TM, Aroian, RV, Ratner, AJ, Role of pore-forming toxins in bacterial infectious diseases. Microbiol Mol Biol Rev 77 (2013), 173–207.
2. Hirst, RA, Kadioglu, A, O'Callaghan, C, Andrew, PW, The role of pneumolysin in pneumococcal pneumonia and meningitis. Clin Exp Immunol 138 (2004), 195–201.
3. Nau, R, Eiffert, H, Minimizing the release of proinflammatory and toxic bacterial products within the host: a promising approach to improve outcome in life-threatening infections. FEMS Immunol Med Microbiol 44 (2005), 1–16.
4. Otto, M, Staphylococcus aureus toxins. Curr Opin Microbiol 17 (2014), 32–37.
5. Baumgartner, D, Aebi, S, Grandgirard, D, et al. Clinical Streptococcus pneumoniae isolates induce differing CXCL8 responses from human nasopharyngeal epithelial cells which are reduced by liposomes. BMC Microbiol 16 (2016), 154–160.
6. Henry, BD, Neill, DR, Becker, KA, et al. Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice. Nat Biotechnol 33 (2015), 81–88.
7. Rello, J, Bunsow, E, Perez, A, What if there were no new antibiotics? A look at alternatives. Expert Rev Clin Pharmacol 9 (2016), 1547–1555.
8. Wolfmeier, H, Radecke, J, Schoenauer, R, et al. Active release of pneumolysin prepores and pores by mammalian cells undergoing a Streptococcus pneumoniae attack. Biochim Biophys Acta 1860 (2016), 2498–2509.
9. Simons, K, Ikonen, E, Functional rafts in cell membranes. Nature 387 (1997), 569–572.
10. Blasi, F, Mantero, M, Santus, P, Tarsia, P, Understanding the burden of pneumococcal disease in adults. Clin Microbiol Infect 18:suppl 5 (2012), 7–14.
11. Capelastegui, A, España, PP, Bilbao, A, et al. Etiology of community-acquired pneumonia in a population-based study: link between etiology and patients characteristics, process-of-care, clinical evolution and outcomes. BMC Infect Dis 12 (2012), 134–143.
12. Jain, S, Self, WH, Wunderink, RG, et al. Community-acquired pneumonia requiring hospitalization among US adults. N Engl J Med 373 (2015), 415–427.
13. Torres, A, Community-acquired pneumonia: changing paradigms about mortality. Community Acquir Infect 1 (2014), 1–3.
14. Mongardon, N, Max, A, Bouglé, A, et al. Epidemiology and outcome of severe pneumococcal pneumonia admitted to intensive care unit: a multicenter study. Crit Care, 16, 2012, R155.
15. Welte, T, Torres, A, Nathwani, D, Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax 67 (2012), 71–79.
16. Musher, DM, Thorner, AR, Community-acquired pneumonia. N Engl J Med 371 (2014), 1619–1628.
17. Torres, A, Peetermans, WE, Viegi, G, Blasi, F, Risk factors for community-acquired pneumonia in adults in Europe: a literature review. Thorax 68 (2013), 1057–1065.
18. Lucas, R, Czikora, I, Sridhar, S, et al. Mini-review: novel therapeutic strategies to blunt actions of pneumolysin in the lungs. Toxins 5 (2013), 1244–1260.
19. EMEA. Guideline on Data Monitoring Committees (EMEA/CHMP/EWP/5872/03). https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-data-monitoring-committees_en.pdf. (Accessed 20 April 2019)
20. Bitounis, D, Fanciullino, R, Iliadis, A, Ciccolini, J, Optimizing druggability through liposomal formulations: new approaches to an old concept. ISRN Pharm, 2012, 2012, 738432.
21. Chang, HI, Yeh, MK, Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy. Int J Nanomedicine 7 (2012), 49–60.
22. Working, PK, Dayan, AD, Pharmacological-toxicological expert report. CAELYX. (Stealth liposomal doxorubicin HCl). Hum Exp Toxicol 15 (1996), 751–785.
23. Soloman, R, Gabizon, AA, Clinical pharmacology of liposomal anthracyclines: focus on pegylated liposomal doxorubicin. Clin Lymphoma Myeloma 8 (2008), 21–32.
24. Szebeni, J, Muggia, F, Gabizon, A, Barenholz, Y, Activation of complement by therapeutic liposomes and other lipid excipient-based therapeutic products: prediction and prevention. Adv Drug Deliv Rev 63 (2011), 1020–1030.
25. Cullis, PR, Chonn, A, Semple, SC, Interactions of liposomes and lipid-based carrier systems with blood proteins: relation to clearance behaviour in vivo. Adv Drug Deliv Rev 32 (1998), 3–17.
26. Szebeni, J, Baranyi, L, Savay, S, et al. Liposome-induced pulmonary hypertension: properties and mechanism of a complement-mediated pseudoallergic reaction. Am J Physiol Heart Circ Physiol 279 (2000), H1319–H1328.
27. Gilbert, RJ, Pore-forming toxins. Cell Mol Life Sci 59 (2002), 832–844.
28. Leung, C, Dudkina, NV, Lukoyanova, N, et al. Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin. Elife, 3, 2014, e04247.