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Journal reading

Efficacy And Safety Of Intravenous


Paracetamol In Comparison To Ibuprofen For
The Treatment Of Patent Ductus Arteriosus
In Preterm Infants: Study Protocol For A
Randomized Control Trial
Pembimbing : dr. Devi Gusmayanto, Sp.A

Oleh
Tommy arean
Latar belakang
PDA (Patent ductus Arteriosus)
Komplikasi RDS pada bayi prematur
60 - 70% obat atau pembedahan
RDS + PDA gagal napas, PIV,BPD,
NET
NSAID dan Ligasi
NSAID
Standarnya : indometasin dan ibuprofen

Keberhasilan 70-80%

Efek samping
Ggn sal. Cerna (perforasi)
Gagal ginjal akut

Gangguan agregasi platelet

Hiperbilirubinemia (ibuprofen)

Pilihan terapi lain > efektif dan aman


Paracetamol
Efektifitas (89%)

Keamanan
Perdarahan GIT dan hiperbilirubinemia

Intravena VS oral paracetamol

Secara farmakodinamik lebih baik

Kandidat yg lebih aman dan efektif


Desain penelitian
Randomized, open-label, parallel-
group, ibuprofen controlled,
multicenter, prospective study
Selama 12 bulan

5 NICU di italia
Kriteria inklusi
Usia kehamilan 25 +0 hingga 31 +6 mgg dan

Inform consent dan

Bukti echocardiografik HsPDA pada usia 24 and 72


jam .

Diagnosis HsPDA pada echo


ductal left-to-right shunt,

with a left atrium-to aortic root ratio >1.3 or a ductal size


>1.5 mm

restrictive PDA being excluded


Kriteria eksklusi
Major congenital malformations and disorders.

Fetal hydrops.

Life-threatening infection, defined as positive blood culture

sample at birth.

Echocardiographic evidence of pulmonary hypertension

diagnosed when the presence of a right-to-left shunt through

the foramen ovale or ductus arteriosus is demonstrated, or

the estimated pulmonary pressure from the tricuspid

regurgitation jet is more than two-thirds the systemic arterial

pressure.
Serum creatinine concentration >1.5 mg/dl (132 mol/l).

Urine output <1 ml/kg/h during a 24-h collection period or urine

output <0.5 ml/kg/h during the first 24 h of life.

Platelet count <50,000/mm3

Major bleeding, as revealed by hematuria, or blood in the

endotracheal aspirate, gastric aspirate,or stools, or consistent

blood oozing from puncture sites.

Severe liver failure, defined as elevated liver enzymes (ALT/GPT

and AST/GOT) >2 times the upper boundary of the normal range.

For this kindof population, the following ranges are considered

normal: ALT/GPT: 650 U/L and AST/GOT: 35140 U/L [34].

Participation in another trial involving any investigational drug.

Previous treatment with paracetamol, ibuprofen, or any COX


Perlakuan
Kelompok 1 Kelompok 2
intravenous solution intravenous solution (5
(10 mg/ml) of mg/ml) of
paracetamol ibuprofen(Pedea,
(Tachipirina, Angelini Orphan Europe, Puteaux

S.p.A., Ancona, Italy) la Defense, France)

15mg/kg/6jam selama Dosis


Awal : 10 mg/kg
3hari
Lanjut : 5 mg /kg
Terapi cairan : 70-80 ml/kg (awal) dinaikkan 10-
20ml/kg/hari dengan target 150-160ml/kg pada
minggu pertama kehidupan.
For the treatment of RDS, infants will receive
oxygen therapy, respiratory support, and rescue
surfactant treatment
PaO2 5060 mmHg, PaCO2 <65 mmHg, pH>7.20, and
SpO2 9095 %

Pemberian antibiotik profilaksis 3-4 hari dan


dihentikan bila kultur bakteri (-)
outcomes
Primary endpoint
Penutupan ductus arteriosus pada terapi tahap awal

Secondary endpoint
Closure rate of PDA after the first and second day of the first treatment course

Closure rate of PDA after the second course of treatment with ibuprofen

Re-opening rate of PDA

Incidence of surgical ligation

Incidence of renal failure, liver failure, and gastrointestinal complications (NEC

and isolated perforation) within 30 days. For study purposes, the renal failure is

defined as a serum creatinine concentration >1.5 mg/dl (132 mol/l) and urine

output <1 ml/kg/h during a 24-h collection period. Liver failure is defined as

elevated liver enzymes more than two times the upper boundary of the normal

range (normal ranges: ALT/GPT = 650 U/L and AST/GOT = 35140 U/L) [34].
PATIENT TIMELINE
Uji statistik
Karakterisitik klinis :
Rerata, median, range, frekuensi dan
persentase

Analisis univariat
T test (parametrik)

Wilcoxon rank sum test (nonparametrik)


Besar sampel
kami menggunakan tes 2 untuk
menghitung bahwa ukuran sampel 49
pasien yang dievaluasi per kelompok
Hipotesa tingkat drop-out 10%

Maka dibutuhkan 55 bayi dalam


setiap kelompok
Pembahasan
Paracetamol pilihan terapi PDA yang sangat
menjanjikan namun masih membutuhkan penelitian
Waktu pemberian obat

Early vs late
Rejimen dosis analgesik yang biasa diberikan di NICU
dan toleransinya baik
Paracetamol dapat menjadi pilihan terapi HsPDA, terutama
karena rendahnya efek samping.