Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of pneumocystis carinii pneumonia in patients with aids: A prospective, controlled multicenter investigation of the aids clinical trials group protocol 029/031

Fred R. Sattler; Peter Frame; Roger Davis; Larry Nichols; Brent Shelton; Bisher Akil; Robert Baughman; Claire Hughlett; Walter Weiss; Charles Van der Horst; John Black; William Powderly; Roy T. Steigbigel; John M. Leedom; Henry Masur; Judith Feinberg; Eyster Elaine; S. Milton; Gocke David; Beck Keith; Lederman Michael; Phair John; Reichman Richard; S. Sacks Henry

doi:10.1093/infdis/170.1.165

Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of pneumocystis carinii pneumonia in patients with aids: A prospective, controlled multicenter investigation of the aids clinical trials group protocol 029/031

Fred R. Sattler
, Peter Frame
, Roger Davis
, Larry Nichols
, Brent Shelton
, Bisher Akil
, Robert Baughman
, Claire Hughlett
, Walter Weiss
, Charles Van der Horst
, John Black
, William Powderly
, Roy T. Steigbigel
, John M. Leedom
, Henry Masur
, Judith Feinberg
, Eyster Elaine
, S. Milton
, Gocke David
, Beck Keith

Lederman Michael, Phair John, Reichman Richard, S. Sacks Henry

Internal Medicine

Producción científica: Article › revisión exhaustiva

99 Citas (Scopus)

Resumen

Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a doubleblind study of trimetrexate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) for 21 days. By study day 10, study therapy failed because of lack of efficacy in 16% of patients assigned to TMP-SMZ and 27% assigned to trimetrexate (P =.064), and the Pao₂ Pao₂ improved significantly faster with TMP-SMZ. By study day 21, failure rates were 20% with TMP-SMZ and 38% with trimetrexate (P =.008), with respective mortality rates of 12% and 20% (P =.088). By study day 49, the difference in mortality (16% vs. 31%) was significant (P =.028). The cumulative incidence of serious and treatment-terminating adverse events including hematologic toxicities was less with trimetrexate (P <.001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, Jor moderately severe P. carinii pneumonia but was better tolerated than TMP-SMZ.

Idioma original	English
Páginas (desde-hasta)	165-172
Número de páginas	8
Publicación	Journal of Infectious Diseases
Volumen	170
N.º	1
DOI	https://doi.org/10.1093/infdis/170.1.165
Estado	Published - jul 1994

Nota bibliográfica

Funding Information:
Received 28 September \993; revised 3\ January 1994. Presented in part: First International Congress of Drug Therapy in HIV Infection, November 1992. Glasgow. Scotland. Sattler F, Davis R. Frame P. Nichols L, Feinberg J. Trimetrexate versus trimethoprim-sulfamethoxazole for severe episodes of Pneumocvstis carinii pneumonia (PCP). AIDS 1992;6(suppl I):S8, 0-8A5. Institutional review board approval was obtained at each ofthe participating centers. and written informed consent was obtained from all study participants or their designated conservators. All investigators are members of the AIDS Clinical Trials Group and receive grant support through a cooperative agreement with the Division of AIDS, National Institutes of Health and University of Southern California (AI-6540). Reprints or correspondence: Dr. Fred R. Sattler. LAC-USC Medical Center. Rand Schrader Clinic, Rm. 349. 1175 N. Cummings St., Los Angeles, CA 90033. * Present affiliation: Division of General Medicine and Primary Care, Beth Israel Hospital, Boston. t Members are listed after text.

Financiación

Received 28 September \993; revised 3\ January 1994. Presented in part: First International Congress of Drug Therapy in HIV Infection, November 1992. Glasgow. Scotland. Sattler F, Davis R. Frame P. Nichols L, Feinberg J. Trimetrexate versus trimethoprim-sulfamethoxazole for severe episodes of Pneumocvstis carinii pneumonia (PCP). AIDS 1992;6(suppl I):S8, 0-8A5. Institutional review board approval was obtained at each ofthe participating centers. and written informed consent was obtained from all study participants or their designated conservators. All investigators are members of the AIDS Clinical Trials Group and receive grant support through a cooperative agreement with the Division of AIDS, National Institutes of Health and University of Southern California (AI-6540). Reprints or correspondence: Dr. Fred R. Sattler. LAC-USC Medical Center. Rand Schrader Clinic, Rm. 349. 1175 N. Cummings St., Los Angeles, CA 90033. * Present affiliation: Division of General Medicine and Primary Care, Beth Israel Hospital, Boston. t Members are listed after text.

Financiadores	Número del financiador
National Institutes of Health and University of Southern California	AI-6540

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

General Medicine

Acceder al documento

10.1093/infdis/170.1.165

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Profundice en los temas de investigación de 'Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of pneumocystis carinii pneumonia in patients with aids: A prospective, controlled multicenter investigation of the aids clinical trials group protocol 029/031'. En conjunto forman una huella única.

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Sattler, F. R., Frame, P., Davis, R., Nichols, L., Shelton, B., Akil, B., Baughman, R., Hughlett, C., Weiss, W., Van der Horst, C., Black, J., Powderly, W., Steigbigel, R. T., Leedom, J. M., Masur, H., Feinberg, J., Elaine, E., Milton, S., David, G., ... Henry, S. S. (1994). Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of pneumocystis carinii pneumonia in patients with aids: A prospective, controlled multicenter investigation of the aids clinical trials group protocol 029/031. Journal of Infectious Diseases, 170(1), 165-172. https://doi.org/10.1093/infdis/170.1.165

Sattler, Fred R. ; Frame, Peter ; Davis, Roger et al. / Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of pneumocystis carinii pneumonia in patients with aids : A prospective, controlled multicenter investigation of the aids clinical trials group protocol 029/031. En: Journal of Infectious Diseases. 1994 ; Vol. 170, N.º 1. pp. 165-172.

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title = "Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of pneumocystis carinii pneumonia in patients with aids: A prospective, controlled multicenter investigation of the aids clinical trials group protocol 029/031",

abstract = "Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a doubleblind study of trimetrexate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) for 21 days. By study day 10, study therapy failed because of lack of efficacy in 16\% of patients assigned to TMP-SMZ and 27\% assigned to trimetrexate (P =.064), and the Pao2 Pao2 improved significantly faster with TMP-SMZ. By study day 21, failure rates were 20\% with TMP-SMZ and 38\% with trimetrexate (P =.008), with respective mortality rates of 12\% and 20\% (P =.088). By study day 49, the difference in mortality (16\% vs. 31\%) was significant (P =.028). The cumulative incidence of serious and treatment-terminating adverse events including hematologic toxicities was less with trimetrexate (P <.001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, Jor moderately severe P. carinii pneumonia but was better tolerated than TMP-SMZ.",

author = "Sattler, \{Fred R.\} and Peter Frame and Roger Davis and Larry Nichols and Brent Shelton and Bisher Akil and Robert Baughman and Claire Hughlett and Walter Weiss and \{Van der Horst\}, Charles and John Black and William Powderly and Steigbigel, \{Roy T.\} and Leedom, \{John M.\} and Henry Masur and Judith Feinberg and Eyster Elaine and S. Milton and Gocke David and Beck Keith and Lederman Michael and Phair John and Reichman Richard and Henry, \{S. Sacks\}",

note = "Funding Information: Received 28 September \textbackslash{}993; revised 3\textbackslash{} January 1994. Presented in part: First International Congress of Drug Therapy in HIV Infection, November 1992. Glasgow. Scotland. Sattler F, Davis R. Frame P. Nichols L, Feinberg J. Trimetrexate versus trimethoprim-sulfamethoxazole for severe episodes of Pneumocvstis carinii pneumonia (PCP). AIDS 1992;6(suppl I):S8, 0-8A5. Institutional review board approval was obtained at each ofthe participating centers. and written informed consent was obtained from all study participants or their designated conservators. All investigators are members of the AIDS Clinical Trials Group and receive grant support through a cooperative agreement with the Division of AIDS, National Institutes of Health and University of Southern California (AI-6540). Reprints or correspondence: Dr. Fred R. Sattler. LAC-USC Medical Center. Rand Schrader Clinic, Rm. 349. 1175 N. Cummings St., Los Angeles, CA 90033. * Present affiliation: Division of General Medicine and Primary Care, Beth Israel Hospital, Boston. t Members are listed after text.",

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doi = "10.1093/infdis/170.1.165",

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Sattler, FR, Frame, P, Davis, R, Nichols, L, Shelton, B, Akil, B, Baughman, R, Hughlett, C, Weiss, W, Van der Horst, C, Black, J, Powderly, W, Steigbigel, RT, Leedom, JM, Masur, H, Feinberg, J, Elaine, E, Milton, S, David, G, Keith, B, Michael, L, John, P, Richard, R & Henry, SS 1994, 'Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of pneumocystis carinii pneumonia in patients with aids: A prospective, controlled multicenter investigation of the aids clinical trials group protocol 029/031', Journal of Infectious Diseases, vol. 170, n.º 1, pp. 165-172. https://doi.org/10.1093/infdis/170.1.165

Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of pneumocystis carinii pneumonia in patients with aids: A prospective, controlled multicenter investigation of the aids clinical trials group protocol 029/031. / Sattler, Fred R.; Frame, Peter; Davis, Roger et al.
En: Journal of Infectious Diseases, Vol. 170, N.º 1, 07.1994, p. 165-172.

Producción científica: Article › revisión exhaustiva

TY - JOUR

T1 - Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of pneumocystis carinii pneumonia in patients with aids

T2 - A prospective, controlled multicenter investigation of the aids clinical trials group protocol 029/031

AU - Sattler, Fred R.

AU - Frame, Peter

AU - Davis, Roger

AU - Nichols, Larry

AU - Shelton, Brent

AU - Akil, Bisher

AU - Baughman, Robert

AU - Hughlett, Claire

AU - Weiss, Walter

AU - Van der Horst, Charles

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AU - Steigbigel, Roy T.

AU - Leedom, John M.

AU - Masur, Henry

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AU - Elaine, Eyster

AU - Milton, S.

AU - David, Gocke

AU - Keith, Beck

AU - Michael, Lederman

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AU - Richard, Reichman

AU - Henry, S. Sacks

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N2 - Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a doubleblind study of trimetrexate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) for 21 days. By study day 10, study therapy failed because of lack of efficacy in 16% of patients assigned to TMP-SMZ and 27% assigned to trimetrexate (P =.064), and the Pao2 Pao2 improved significantly faster with TMP-SMZ. By study day 21, failure rates were 20% with TMP-SMZ and 38% with trimetrexate (P =.008), with respective mortality rates of 12% and 20% (P =.088). By study day 49, the difference in mortality (16% vs. 31%) was significant (P =.028). The cumulative incidence of serious and treatment-terminating adverse events including hematologic toxicities was less with trimetrexate (P <.001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, Jor moderately severe P. carinii pneumonia but was better tolerated than TMP-SMZ.

AB - Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a doubleblind study of trimetrexate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) for 21 days. By study day 10, study therapy failed because of lack of efficacy in 16% of patients assigned to TMP-SMZ and 27% assigned to trimetrexate (P =.064), and the Pao2 Pao2 improved significantly faster with TMP-SMZ. By study day 21, failure rates were 20% with TMP-SMZ and 38% with trimetrexate (P =.008), with respective mortality rates of 12% and 20% (P =.088). By study day 49, the difference in mortality (16% vs. 31%) was significant (P =.028). The cumulative incidence of serious and treatment-terminating adverse events including hematologic toxicities was less with trimetrexate (P <.001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, Jor moderately severe P. carinii pneumonia but was better tolerated than TMP-SMZ.

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Sattler FR, Frame P, Davis R, Nichols L, Shelton B, Akil B et al. Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of pneumocystis carinii pneumonia in patients with aids: A prospective, controlled multicenter investigation of the aids clinical trials group protocol 029/031. Journal of Infectious Diseases. 1994 jul;170(1):165-172. doi: 10.1093/infdis/170.1.165