Retracted: Nifedipine alone or combined with sildenafil citrate for management of threatened preterm labour: a randomised trial

Abstract

Objective To study the tocolytic action of nifedipine combined with sildenafil citrate (SC) and if the combination is superior to nifedipine alone in inhibiting threatened preterm labour (PTL). Design Prospective randomised study. Setting An Egyptian university hospital. Population Women with threatened PTL who received either nifedipine with SC or nifedipine alone. Methods Patients were randomly allocated to receive either (1) nifedipine 20 mg orally (stat dose), followed by 10 mg orally every 6–8 hours at the same time as vaginal administration of SC (25 mg at 8‐hourly intervals) or (2) nifedipine alone. Medications were continued for 48–72 hours. Main outcome measures The percentage of women who remained undelivered during hospitalisation. Results From January 2015 to November 2016, 239 women were randomised. The baseline characteristics of participants were similar. Nifedipine combined with SC was associated with more women remaining undelivered (81.8 versus 68.6%; P = 0.018) during hospitalisation. Regarding secondary outcomes, the addition of SC was also associated with fewer deliveries within 7 days of admission (9.1 versus 20.3%; P = 0.014), prolonged latency (29 versus 7 days; P = 0.002), fewer admissions to neonatal intensive care units (31.4 versus 44.1%; P = 0.043), fewer very preterm deliveries (from 28 to <32 weeks, 20.7 versus 38.1%; P = 0.043), and increased neonatal birthweight (1900 versus 1500 g; P = 0.018). Conclusions Vaginal SC combined with nifedipine is an effective option for tocolytic therapy during threatened PTL. Tweetable abstract Vaginal SC enhances the tocolytic effect of nifedipine.

Tocolytic effect of combined sildenafil citrate and nifedepine versus nifedipine alone for management of preterm labour at a tertiary centre

“…Maher et al in their trial had shown superior tocolytic effect of nifedipine and sildenafil citrate combination to that of nifedipine alone. 2 In current study we have also observed superior efficacy of nifedipine and sildenafil citrate combination as compared to nifedipine alone in terms of inhibiting preterm labour and improving perinatal outcomes.…”

“…12 Maher et al also referred higher latency in nifedipine and sildenafil citrate group. 2 In contrast, Ali et al had also documented nearly same relaxing effect of both sildenafil and nifedipine on myometrium to prevent preterm birth. 7 In recent study fewer deliveries occurred during hospitalization or within 7 days after discharge hence more women remains undelivered in combination regimen.…”

“…7 Similar trial was also conducted by El-Far et al, Maher et al and Khan et al in which vaginal route for sildenafil citrate was preferred. 2,8,9 Total mean dose of nifedipine in both the regimens were 134.5±16.94 and 131.0±23.07 mg. None of the participant required repeated dose of any regimen. Maher et al in their trial had shown superior tocolytic effect of nifedipine and sildenafil citrate combination to that of nifedipine alone.…”

“…tocolytics agents while another meta-analysis recommended it as drug of choice for threatened preterm labour. 2,3 Sildenafil, the citrate salt of 1-(4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo(4,3-d) pyrimidine-5-phenyl-sulphonyl) -4-methylpiperazine prevent the degradation of second messenger cyclic guanosine 3',5'-monophosphate by the enzyme PDE-5 which increased nitric oxide production and consequent vascular smooth muscle relaxation and vasodilation. 6 The relaxant action of cGMP in smooth muscle, through its downstream effector the enzyme protein kinase G, results in reduced intracellular calcium levels and a reduced sensitivity of the contractile elements to calcium.…”

“…The vasodilator effect of sildenafil citrate also manifested on uterine and myometrial vessels result in increased uterine flow and endometrial thickening, putatively promoting an increase in fetal weight. 2,4,5 To date, very few studies have explored the tocolytic effect of sildenafil and the use of sildenafil citrate in human pregnancy has been confirmed to relatively small RCTs and reports. Further availability of slow and sustained release preparations, low incidence of side effects, limited cost and ease of administration as compared to other tocolytics, attracted our attention to use the medication for preterm labour.…”