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Table 1 Study characteristic animal studies

From: Antileukotrienes for the prevention and treatment of chronic lung disease in very preterm newborns: a systematic review

  Prevention studies (antileukotrienes are administered before inducing lung or systemic damage) Studies on both prevention and treatment (antileukotrienes are administered before and after inducing lung or systemic damage) Treatment studies (antileukotrienes are administered after inducing lung or systemic damage)
Demir 2008 Kertesz 1992 Cassin 1989 Phillips 1995 Schreiber 1985 Schreiber 1987 Xiao-Yan 2020 Chen 2018 Jouvencel 2003 Park 2011
Study design* Experimental Experimental Observational Experimental Observational Observational Experimental Experimental Experimental Experimental
Total number of animals at the very beginning 47 Not reported 24 lambs
10 goats
Not reported 6 16 72 45 24 Not reported
Number of animals which received antileukotrienes Montelukast group n = 10
clarithromycin + montelukast + pentoxifylline combination group n = 6
(plus other study groups not relevant in this review)
Experiment 1: 31
0.1 uM/kg/h: 4 + 1 + 3 + 6 = 14
1.0 uM/kg/h: 8 + 9 = 17
experiment 2: not reported
Not reported Prevention (normoxia): 19 (with three different doses)
Treatment (hyperoxia): 22
5 (we use experiment FPL 57,231 infusion started during hypoxia, so exp 2) 5 24 Not reported 12 Not reported
Number of animals in control group Clarithromycin n = 8
pentoxifylline n = 8
placebo n = 6
Experiment 1: 2 + 2 + 11 + 12 = 27
experiment 2: 60
No control group, i.e. all animals got antileukotrienes Prevention (normoxia): 6
Treatment (hyperoxia): 6
No control group, i.e. all animals got antileukotrienes No control group, i.e. all animals got antileukotrienes 24 Not reported 12 Not reported
Number of animals outcome data are reported for 47 Not reported Sheep: 16 for antileukotrienes (plus 3 for thromboxane receptor antagonist)
goats: 6 for antileukotrienes (plus 4 for thromboxane receptor antagonist)
Not reported Not reported Not reported 72 Not reported 16 Not reported
Funding Supported by Dokuz Eylul University and The Scientific and Technological Research Council of Turkey Antileuk provided by Stuart Pharmaceuticals
Study partly supported by the Dee and Moody Research Fund of Evanston Hospital
National Hear, Lung and Blood institute Grant
Antileukotrienes provided by the pharma
Supported by the Medical Research Council
Drug provided by Upjohn Company
Supported in part by grants from the American Lung Association and U.S.Public Health Service Program Project Grant HL 24,056 Supported in part by grants from the American Lung Association, HL35518, and US Public Health Service Program Project Grant HL24056 Funded by Jiangsu Provincial Maternal and Child Health Research Project (F201647 Funding Project of Bengbu Medical College of Science and Technology Development (No. BYKF1741) Grant sponsor: Société Française de Médecine Néonatale; Montelukast sodium a gift from Merck, Sharp and Dohme, Whitehouse Station, NJ Medical Grant Program of Merck Sharp and Dohme Corp. (Rahway, NJ, USA), who also supplied with MK-0591 in powder form
Species Rats Rabbits Sheep, goats Guinea pig Lambs Lambs Rats Mice Rats Mice
Strain Wistar New Zealand albino Not reported Not reported Mixed-breed Not reported Clean level P3 SD 57BL/6 J Wistar FVB/n
Age when antileuk/comparator were given Postnatal days 3–13 day 7 Five days. Unclear, but it is likely that the animals were given antileukotrienes and were exposed to hypoxia at the same day day 3–6 day 3–7 day 4–6 Not reported day 2–14 day 4 Treatment windows were from days 1–4, 5–9 or 10–14 after birth
Presence and degree of prematurity Full term Full term Not reported Pre-term Not reported Not reported Likely Full term Likely Full term Likely Full term Full term
Mode of delivery Naturally delivered Not reported Not reported Caesarean section Not reported Not reported Not reported Not reported Not reported Naturally delivered
Type of lung damage/insult Hyperoxia Hyperoxia > 95% O2 Hypoxia, ventilation Hyperoxia 95%O2 Hypoxia LTD4 injection Hypoxia Hyperoxia Hyperoxia 50% O2 from P0 to P15 Hyperoxia 85% O2
Age at lung damage Days 3–13 Day 7 Five days. Unclear, but it is likely that the animals were given antileukotrienes and were exposed to hypoxia at the same day days 1–3 Days 3–7 Days 4–6 Not reported 12 h, hyperoxia for 7 consecutive days Within 24 h of birth Within 24 h of birth
Type of control group Clarithromycin
Pentoxifylline
Placebo
Vehicle No control group, i.e. all animals got antileukotrienes Vehicle No control group, i.e. all animals got antileukotrienes No control group, i.e. all animals got antileukotrienes Saline for periventricular leukomalacia group Saline (0.9% NaCl) Saline Vehicle
(5% ethanol; 1% Tween 80)
Name of antileuk/name of comparator Antileuk:
Montelukast,
Montelukast + pentoxifylline + clarithromycin combination
Comparator:
clarithromycin
pentoxifylline
INTERVENTION
ICI 198,615 (leukotriene receptor antagonist)
CONTROL
vehicle consisting of polyethylene glycol 400
(PEG 4OO), 1 M NaOH, and phosphate buffered
saline (PBS)
Leukotriene receptor antagonist L 649923
Dual cyclooxygenease and lipoxygenase inhibitor BW 755C
U-75302 (LTB4 antagonist) FPL57231 (leukotriene receptor antagonist) FPL57231 (leukotriene receptor antagonist) INTERVENTION
Pranlukast
CONTROL
Saline
Antileuk: montelukast sodium
Control:
Saline
INTERVENTION
Montelukast sodium
CONTROL
Normal saline
INTERVENTION
MK-0591 (5-lipoxygenase-activating protein inhibitor)
CONTROL
vehicle
Dose INTERVENTION
montelukast: 1 mg/kg/day one dose
combination: clarithromycin 100 mg/kg in two doses per day, montelukast 1 mg/kg/day, pentoxifylline 150 mg/kg in two doses per day
CONTROL
clarithromycin: 100 mg/kg/day in two doses
pentoxifylline: 150 mg/kg/day in two doses
saline: not reported
INTERVENTION
experiment 1: two groups
group 1: 0.1 uM/kg/h ICI
group 2: 1.0 uM/kg/h ICI
Experiment 2: 0.1 uM/kg/h
CONTROL
not reported
L 649,923: prepared in saline daily (10 mg/ml) and injected (5,86 mg/kg) over a 2 min period
BW 755C: prepared in saline (8,8 mg/ml) and administered (30 mg/kg) over a 2- to 5-min period
3.0 mg/100 g body wt** 2 mg/kg/min (total 20 mg/kg) 2 mg/kg/min (total 20 mg/kg) 0.1 mg/kg Montelukast
10 mg/kg
Saline
not reported
INTERVENTION
1 mg/kg/day (diluted in normal saline to 200mcg/ml—injected 5 mcg/g)
CONTROL
5 mcg/g
INTERVENTION
40 mg/kg **
Frequency INTERVENTION
montelukast: 1 dose per day
combination: clarithromycin in two doses per day, montelukast 1 dose per day, pentoxifylline in two doses per day
CONTROL
clarithromycin: in two doses per day
pentoxifylline: in two doses per day
saline: once daily
Continuous by micro-pump pumping 0.5 uL/h We suspect that the drugs were only given once, but this cannot be extracted from the text with complete certainty Every 12 h over a 72 h period Once for 10 min Once for 10 min once every 12 h, for 3 consecutive days Once every other day 1/day, from days 4–14 Once daily during the treatment window
Route of administration INTERVENTION
subcutaneously
CONTROL
clarithromycin: subcutaneously
pentoxifylline: injected intraperitoneally
saline: not reported
Subcutaneous pump L 649,923: injected directly into the pulmonary circulation
BW 755C: administered via femoral artery
Not reported Infusion Intravenous infusion Intraperitoneal injection Intraperitoneally Subcutaneously Subcutaneously
  1. *Experimental: Compares outcomes with vs without antileuk administration (not all animals received antileuk); Observational: Compares outcomes before vs after antileuk administration (all animals received antileuk)
  2. **The study reports results for different doses
  3. None of the included studies reported on the following characteristics: protocol registration, immune status, sex, initiation dose