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

Internal Medicine

Research output: Contribution to journal › Article › peer-review

96 Scopus citations

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.

Original language	English
Pages (from-to)	165-172
Number of pages	8
Journal	Journal of Infectious Diseases
Volume	170
Issue number	1
DOIs	https://doi.org/10.1093/infdis/170.1.165
State	Published - Jul 1994

Bibliographical note

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.

ASJC Scopus subject areas

Medicine (all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/infdis/170.1.165

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this

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. In: Journal of Infectious Diseases. 1994 ; Vol. 170, No. 1. pp. 165-172.

@article{971e4675fb0f4aa7bf9a384274b26c77,

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 \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.",

year = "1994",

month = jul,

doi = "10.1093/infdis/170.1.165",

language = "English",

volume = "170",

pages = "165--172",

number = "1",

}

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, no. 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.
In: Journal of Infectious Diseases, Vol. 170, No. 1, 07.1994, p. 165-172.

Research output: Contribution to journal › Article › peer-review

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

AU - Black, John

AU - Powderly, William

AU - Steigbigel, Roy T.

AU - Leedom, John M.

AU - Masur, Henry

AU - Feinberg, Judith

AU - Elaine, Eyster

AU - Milton, S.

AU - David, Gocke

AU - Keith, Beck

AU - Michael, Lederman

AU - John, Phair

AU - Richard, Reichman

AU - Henry, S. Sacks

N1 - 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.

PY - 1994/7

Y1 - 1994/7

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.

UR - http://www.scopus.com/inward/record.url?scp=0028364088&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028364088&partnerID=8YFLogxK

U2 - 10.1093/infdis/170.1.165

DO - 10.1093/infdis/170.1.165

M3 - Article

C2 - 8014493

AN - SCOPUS:0028364088

SN - 0022-1899

VL - 170

SP - 165

EP - 172

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 1

ER -

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

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

Bibliographical note

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this