Role of co-trimoxazol prophilaxis in reducing mortaliy in hiv infected adults being treated for tuberculosis : randomized clinical trial

Awang Wibisono Ricki Rizki Wulandari Pawestri Lili Nurhidayati Mutiara Irianda P Nanda Rizki F Priyanka Dyah S Puspita Mahaputri Yudith K Aisyah Zoraya Febriana

1102008276 1102008302 1102008322 1102009162 1102009195 1102009200 1102009222 1102009255 1102009307 1102009310

Figure 1 depicts the flow of participants during the study. Of 1505 people who were known to be HIV positive, 240 did not wish to receive their result; among these, 50 people did not wish to join the trial because they lived too far away, 30 reported that they needed to consult relatives, and 19 thought that their blood would be used for satanic purposes; 115 gave no reason

Tidak
Follow-up We had no information on 78 (37 cotrimoxazole, 41 placebo) (9.3%) participants after randomisation.

Analysis of data We entered all data in duplicate locally and verified them by using Epi-Info software version 6.04d. Master databases were backed up at regular intervals and copies transmitted by electronic mail to the MRC Clinical Trials Unit in London on a monthly basis. We set up trial management committees in London and Lusaka to review the progress of the trial on a regular basis and an independent data monitoring committee to monitor the progress of the trial and patient safety every six to eight months. We did no formal interim analyses. Weused the Kaplan-Meier method, the log rank test, and a Cox proportional hazard regression model to make comparisons of the groups for the primary end point by time to event analyses and tested heterogeneity of survival rates in subgroups by interaction tests within Cox models. We fitted a fractional polynomial model to assess the effect of randomised group over time,16 using a nearly linear pre-transformation to reduce the influence of outliers after a fixed time point.17 We made all comparisons by intention to treat and used Stata version 8 for analyses.

Peneliti dan klinisi sama-sama tidak mengetahui baik itu co-trimokxazole dan placebo

Tidak terdapat persamaan di antara kedua kelompok di awal penelitian , dapat dilihat dari tabel di bawah ini dari berbagai macam karakteristik .

karakteristik Sex: Male Female Age group (yrs) : 15-24 25-34 35-44 45 Mean (SD) weight (kg) : Mean (SD) body mass index :

Co-trimoxazole (n=416) 240 (58) 176 (42) 47 (11) 210 (50) 127 (31) 32(8) 49.5 (7.9) 15.5 (4.7) 195 (47) 22 (55) 185 (44) 223 (54) 12 (3) 3 (1) 5 (1) 16 (4) 2 (0.5) 289 (70) 7 (2)

Placebo (n=419) 226 (54) 193 (46) 59* (14) 211 (50) 122 (29) 27 (6) 49.0 (7.2) 15.2 (4.1) 188 (45) 18 (4) 197 (47) 231 (55) 13 (3) 3 (1) 5(1) 22 (5) 2 (0.5) 269 (64) 9(2)

HIV related symptoms : Fever Diarrhoea Weight loss Persisten cough Painfull genital ulceration Herpes zooster Gnerlised pruritic maculopap rash Oral kandidiasis Kaposis sarcoma Generalised lymphadenopathy Other ADIS symptoms

karakteristik

Co-trimoxazole (n=416)

Placebo (n=419)

CD4 count (cells/10) : 0-49 50-99 100-199 200-299 300

20 (12) 28 (16) 44 (26) 33 (19) 46 (27)

25 (14) 22 (12) 53 (30) 32 (18) 45 (25)

*includes one participant aged 14 yrs Available for 399 Co-trimoxazole and 402 placebo participans Calculated for 396 Co-trimoxazole and 397 placebo participants

Ada. Terutama dalam follow up pasien

TATA CARA PENELITIAN

Pasien dibagi menjadi rasio 1:1 menerima cotrimoxazole (mengandung 400 mg sulfametoksazol dan 80mg trimethoprim) ATAU placebo (masing-masing diminum 2tablet/hari)
Pasien dengan aktif, sebelumnya tidak diobati TBC menerima rejimen standar etambutol,isoniazid, rifampisin, dan pirazinamid selama dua bulan diikuti dengan isoniazid dan etambutol selama enam bulan Pasien yang membutuhkan pengobatan ulang karena kambuh menerima satu dari rekomendasi WHO tentang rejimen pengobatan ulang

jika pasien semakin sakit pengobatan dihentikan dilanjutkan ketika episode akut telah terlewati

Besarnya Efek Terapi Perlakuan pada pasien ada 4 secara acak : 1. Sedang menerima treatment tuberculosis 835 (416 cotrimoxazole dan 419 placebo) 2. Baru di diagnosis sebagai penderita TB HIV tetapi belum mendapat treatment apapun 762 (376 co-trimoxazole dan 386 placebo) 3. Pengobatan ulang 73 (40 co-trimoxazole dan 33 placebo) 4. tidak sedang dalam treatment tetapi telah mendapatkan treatment dulu 168 (84 co-trimoxazole dan 84 placebo)

Menyimpulkan hasil terapi

Total 310 pasien mati saat study ini dimulai. Sekitar 27. 3 setiap 100 orang per tahun pengguna cotrimoxazole, dan 34.4 setiap orang per tahun pengguna placebo. Co-trimoxazole asosiasi dengan penurunan 21% pada semua kasus mortalitas (Hazard ratio 0.79, 95% dengan interval 0.63 sampai 0.99; P=0.04) Pada fig 2 menggunakan plots kaplan meiner untuk semua 835 pasien yang meninggal Analiysis dengan menggunakan CD4 terlihat tidak ada perbedaan dengan level immunosupresan (P>0.5, Test untuk heterogenesitas) Tidak ada perbedaan antara umur atau jenis kelamin.

Ditemukan adanya perbedaan yang signifikan di dalam waktu yang berbeda (P = 0.02). Tidak ada kejaidan yang bermanfaat dalam waktu 6 bulan. Pemanfaatan yang konsisten antara 6-18 bulan. Terjadi penurunan mortalitas sebanyak 45%.

Apakah hasil ini dapat diterapkan untuk pasien saya?

KELEBIHAN Cotrimoxazole menurunkan angka kematian pasien

Assuming a death rate of 15 per 100 person years in the Previously untreated participants (based on a deathrate of 18/100 person years in a trial in a similar population of patients in Lusaka15), a total of 1408 person years of observation would be needed to show a 35%reduction in deathrate in patients receiving co-trimoxazole, at the 5% level of significance with 80% power; a 40% reduction would require 1045 person years.

Co-trimoxazole menurunkan angka kematian pasien

KEKURANGAN Peningkatan resistensi cotrimoxazole jika digunakan dalam jangka panjang Peningkatan resistensi terhadap antimalaria Fansidar (pirimetamin-sulfadoxine)

 Tidak berpengaruh pada kadar sel CD4