Critical Appraisal Worksheet

Jurnal Terapi
Patiromer in Patients with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors

Validitas
Pertanyaan Jawab Jelaskan, dan sebutkan dimana
penjelasan tersebut ditemukan,
tuliskan juga potongan kalimat yang
dimaksud.
1a. Apakah alokasi pasien Ya
terhadap terapi / perlakukan [ ] Ya, Halaman.212
dilakukan secara random ? “Metode: “The study had two phases —
Tidak a 4-week singlegroup,single-blind initial
[ ] treatment phase and an 8-week placebo-
controlled, single-blind, randomized
withdrawal phase.”
1b. Apakah randomisasi dilakukan Ya
tersembunyi ? [ ] Ya, halaman: 212
“The study had two phases — a 4-week
Tidak singlegroup,single-blind initial treatment
[ ] phase and an 8-week placebo-controlled,
single-blind, randomized withdrawal
phase.”

1c. Apakah antara subyek Ya Ya, pada penelitian ini dilakukan single
penelitian dan peneliti ‘blind’ [ ] blind sehingga hanya subjek peneliti
terhadap terapi / perlakukan yang yang tidak tau, halaman: 212
akan diberikan ? Tidak “Here we present the results of a
[ ] multinational, single-blind, two-phase
study evaluating the safety and efficacy
of patiromer in patients with chronic
kidney disease who were receiving at
least one RAAS inhibitor and who had
hyperkalemia.”
Halaman: 212
Metode: “The study had two phases — a
4-week singlegroup,single-blind initial
treatment phase and an 8-week placebo-
controlled, single-blind, randomized
withdrawal phase”.

2a. Apakah semua subyek yang Ya Ya, halaman 215

ikut serta dalam penelitian [ ] Result: “A total of 243 patients were
diperhitungkan dalam hasil / enrolled in the initial treatment phase (92
kesimpulan ? (Apakah Tidak with mild hyperkalemia and 151 with
pengamatannya cukup lengkap?) [ ] moderate-to-severe hyperkalemia) at
sites in Eastern Europe (24 sites), the
European Union (21), and the United
States. All the patients received at least
one dose of patiromer; 24 patients (10%)
discontinued this phase prematurely”. Of
the 219 patients who completed the
initial treatment phase, 109 were not
eligible to enter the randomized
 withdrawal phase, and 3 declined further
participation in the study. The most
common reason for ineligibility was a
baseline potassium level of less than 5.5
mmol per liter, as measured at a central
laboratory (97 patients [89%]). Eight
patients (3 with mild hyperkalemia and 5
with moderate-to-severe hyperkalemia)
were ineligible for randomization in the
randomized withdrawal phase solely on
the basis of a serum potassium level that
was not in the control range at week 4
(Fig. S1 in the Supplementary Appendix).
A total of 107 patients were randomly
assigned to continue patiromer treatment
(55 patients) or to switch to placebo (52
patients).
2b. Apakah pengamatan yang Ya Tidak, karena pada umumnya uji efikasi
dilakukan cukup panjang ? [ ] obat dilakukan dengan jangka waktu
panjang sedangkan pada penelitian ini
Tidak hanya menghabiskan waktu selama 3
[ ] bulan
Halaman: 215 “Figure 1”
Halaman: 216 “Figure 2”
Halaman: 212 Metode: “The study had
two phases — a 4-week
singlegroup,single-blind initial treatment
phase and an 8-week placebo-
controlled, single-blind, randomized
withdrawal phase.”
2c. Apakah subyek dianalisis pada Ya
kelompok dimana subyek tersebut [ ] Ya, Halaman: 217 “Figure 3” and
dikelompokkan dalam “At the start of the randomized
randomisasi ? Tidak withdrawal phase, which included
[ ] patients whose serum potassium level
had been well controlled while they were
receiving patiromer in the initial treatment
phase, the mean potassium level was
4.45 mmol per liter in the group that was
randomly assigned to placebo (52
patients) and 4.49 mmol per liter in the
group that was randomly assigned to
continue patiromer treatment (55
patients)”
Halaman: 218
3a. Selain perlakuan yang Ya
dieksperimenkan, apakah subyek [ ] Ya, pada penelitian ini semua subjek
diperlakukan sama ? diperlakukan sama.
Tidak Halaman: 212 ” All patients provided
[ ] written informed consent”
halaman: 215, “figure 1” Values are the
observed mean values as measured in
a central laboratory. During the 4-week
initial treatment phase, all patients
 received treatment with patiromer;
patients with a potassium level of 5.1 to
less than 5.5 mmol per liter (mild
hyperkalemia) received 4.2 g of
patiromer twice daily, and those with a
potassium level of 5.5 to less than 6.5
mmol per liter (moderateto- severe
hyperkalemia) received 8.4 g of
patiromer twice daily.

3b. Apakah kelompok dalam Ya

penelitian sama pada awal [ ] Ya, sama. Pada penelitian ini dibagi
penelitian ? menjadi 2 fase, yaitu fase pengobatan
Tidak awal dan fase randomize yg terbagi
[ ] menjadi 2 kelompok dengan kriteria
inklusi yang sama menjadi Kelompok
pengobatan petiromer dan kelompok
plasebo.
Halaman.212
“Metode: “The study had two phases —
a 4-week singlegroup,single-blind initial
treatment phase and an 8-week placebo-
controlled, single-blind, randomized
withdrawal phase.”
Halaman: 217 “Figure 3”

Importance
1. Berapa besar efek terapi?
Ya, halaman 211
Result: “In the initial treatment phase, among 237
2. Seberapa tepat estimasi efek patients receiving patiromer who had at least one
terapi ? potassium measurement at a scheduled visit after
day 3, the mean (±SE) change in the serum
potassium level was −1.01±0.03 mmol per liter
(P<0.001). At week 4, 76% (95% confidence
interval, 70 to 81) of the patients had reached the
target potassium level (3.8 to <5.1 mmol per liter).
Subsequently, 107 patients were randomly
assigned to patiromer (55 patients) or placebo (52
patients) for the randomized withdrawal phase.
The median increase in the potassium level
from baseline of that phase was greater with
placebo than with patiromer (P<0.001); a
recurrence of hyperkalemia (potassium level,
≥5.5 mmol per liter) occurred in 60% of the
patients in the placebo group as compared with
15% in the patiromer group through week 8
(P<0.001)”

Conclusions: “In patients with chronic kidney

disease who were receiving RAAS inhibitors and
who had hyperkalemia, patiromer treatment was
associated with a decrease in serum potassium
levels and, as compared with placebo, a
 reduction in the recurrence of hyperkalemia”

Applicable
1. Apakah pasien yang kita miliki Ya
sangat berbeda dengan pasien [ ] Tidak, pasien dalam penelitian telah
dalam penelitian ? dipilih berdasarkan kriteria inklusi
Tidak halaman 212
[ ] “Patients were eligible for inclusion in
the study if they were 18 to 80 years of
age, had stage 3 or 4 chronic kidney
disease (estimated glomerular filtration
rate [eGFR], 15 to <60 ml per minute
per 1.73 m2 of body-surface area), had
serum potassium levels of 5.1 to less
than 6.5 mmol per liter at two
screenings, and had been receiving a
stable dose of one or more RAAS
inhibitors for at least 28 days. Doses of
antihypertensive drugs, loop and
thiazide diuretics, and beta-blockers
had to have been stable for 28 days
before screening.”
Halaman:214  “tabel 1”
Halaman: 217  “figure 3”
2. Apakah hasil yang baik dari Ya
penelitian dapat diterapkan dengan [ ] Ya, halaman.211
kondisi yang kita miliki ? Conclusions: “In patients with chronic
Tidak kidney disease who were receiving
[ ] RAAS inhibitors and who had
hyperkalemia, patiromer treatment
was associated with a decrease in
serum potassium levels and, as
compared with placebo, a reduction
in the recurrence of hyperkalemia”

Halaman: 211
Conclusions: “At week 4, 76% (95%
confidence interval, 70 to 81) of the
patients had reached the target
potassium level (3.8 to <5.1 mmol per
liter). Subsequently, 107 patients were
randomly assigned to patiromer (55
patients) or placebo (52 patients) for the
randomized withdrawal phase. The
median increase in the potassium level
from baseline of that phase was greater
with placebo than with patiromer
(P<0.001); a recurrence of
hyperkalemia (potassium level, ≥5.5
mmol per liter) occurred in 60% of the
patients in the placebo group as
compared with 15% in the patiromer
group through week 8 (P<0.001)”
3. Apakah semua outcome klinis Ya
yang penting dipertimbangkan [ ] Ya, pada penelitian ini mebahas efek
(efek samping yang mungkin samping yang mungkin timbul akibat
timbul)? Tidak penggunaan patiromer.
[ ] Halaman: 218  “tabel 2” dan “tabel 3”
“The most common adverse events are
shown in Table 2; mild-to-moderate
constipation was the most common
adverse event (occurring in 11% of the
patients). The majority of
gastrointestinal adverse events
occurred in less than 2% of the
patients. No serious gastrointestinal
events occurred in this phase. Adverse
events leading to discontinuation of
patiromer occurred in 15 patients (6%).
Three patients (1%) had a total of six
serious adverse events (Table S7 in the
Supplementary Appendix). None were
fatal, and all were considered by the
investigators not to be related to
patiromer treatment”

Halaman 118-119: “During the

randomized withdrawal phase and
through its follow-up period, the
proportion of patients with one or more
adverse events was similar in the
placebo group and the patiromer group
(50% and 47%, respectively). Mild-
tomoderate constipation, diarrhea, and
nausea were the most common
gastrointestinal events reported with
patiromer (each in 4% of the patients);
these events occurred in none of the
patients in the placebo group (Table 3).

Halaman: 220
“Mild-to-moderate constipation, the
most common adverse event with
patiromer (occurring in 11% of the
patients during the initial treatment
phase and in 4% during the randomized
withdrawal phase), generally did not
limit treatment. The rates of all other
adverse events with patiromer were
low and similar to those with placebo
in the randomized withdrawal phase.
Few serious adverse events occurred;
investigators, who were aware of the
treatment assignments, attributed none
of these events to patiromer”
4. Apakah sudah memahami Ya
harapan dan pilihan pasien ? [ ] Ya, halaman 211
Conclusions: “In patients with chronic
 Tidak kidney disease who were receiving
[ ] RAAS inhibitors and
who had hyperkalemia, patiromer
treatment was associated with a
decrease in serum potassium levels
and, as compared with placebo, a
reduction in the recurrence of
hyperkalemia”

5. Apakah intervensi yang akan Ya Ya, halaman: 220

diberikan akan memenuhi harapan [ ] “among patients with chronic kidney
pasien ? Pasien siap akan disease who were taking RAAS
konsekuensinya? Tidak inhibitors and who had hyperkalemia,
[ ] treatment with patiromer was
associated with reductions in serum
potassium levels and maintenance of
normal potassium levels”

Ya, Semua pasien telah diberikan

informed consent tertulis.
Halaman : 212
The protocol was approved by the local
or central institutional review board or
ethics committee for each participating
center. All patients provided written
informed consent; the study was
performed in accordance with the
International Conference on
Harmonisation Guidelines for Good
Clinical Practice.