Hypotension in Preterm Infants (HIP) randomised trial.
Ontology highlight
ABSTRACT: Objective
To determine whether restricting the use of inotrope after diagnosis of low blood pressure (BP) in the first 72 hours of life affects survival without significant brain injury at 36 weeks of postmenstrual age (PMA) in infants born before 28 weeks of gestation.Design
Double-blind, placebo-controlled randomised trial. Caregivers were masked to group assignment.Setting
10 sites across Europe and Canada.Participants
Infants born before 28 weeks of gestation were eligible if they had an invasive mean BP less than their gestational age that persisted for ≥15 min in the first 72 hours of life and a cerebral ultrasound free of significant (≥ grade 3) intraventricular haemorrhage.Intervention
Participants were randomly assigned to saline bolus followed by either a dopamine infusion (standard management) or placebo (5% dextrose) infusion (restrictive management).Primary outcome
Survival to 36 weeks of PMA without severe brain injury.Results
The trial terminated early due to significant enrolment issues (7.7% of planned recruitment). 58 infants were enrolled between February 2015 and September 2017. The two groups were well matched for baseline variables. In the standard group, 18/29 (62%) achieved the primary outcome compared with 20/29 (69%) in the restrictive group (p=0.58). Additional treatments for low BP were used less frequently in the standard arm (11/29 (38%) vs 19/29 (66%), p=0.038).Conclusion
Though this study lacked power, we did not detect major differences in clinical outcomes between standard or restrictive approach to treatment. These results will inform future studies in this area.Trial registration number
NCT01482559, EudraCT 2010-023988-17.
SUBMITTER: Dempsey EM
PROVIDER: S-EPMC8237176 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundInfections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications. The aim of this large randomised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice.MethodsIn this randomised placebo-controlled trial, we recruited very preterm infants born before 32 weeks' gestation in 37 UK hospitals and younger than 72 h at randomisation. Exclusion criteria were presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival. Eligible infants were randomly assigned (1:1) to receive either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age. Web-based randomisation minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers, and outcome assessors were unaware of group assignment. The primary outcome was microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth), which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. The trial is registered with the International Standard Randomised Controlled Trial Number 88261002.FindingsWe recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86-1·04; p=0·233). During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group. Two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation) were assessed as being possibly related to the trial intervention.InterpretationEnteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants. These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants.FundingUK National Institute for Health Research Health Technology Assessment programme (10/57/49).
| S-EPMC6356450 | biostudies-literature
Project description:ObjectiveTo test whether azithromycin eradicates Ureaplasma from the respiratory tract in preterm infants.DesignProspective, phase IIb randomised, double-blind, placebo-controlled trial.SettingSeven level III-IV US, academic, neonatal intensive care units (NICUs).PatientsInfants 240-286 weeks' gestation (stratified 240-266; 270-286 weeks) randomly assigned within 4 days following birth from July 2013 to August 2016.InterventionsIntravenous azithromycin 20 mg/kg or an equal volume of D5W (placebo) every 24 hours for 3 days.Main outcome measuresThe primary efficacy outcome was Ureaplasma-free survival. Secondary outcomes were all-cause mortality, Ureaplasma clearance, physiological bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age, comorbidities of prematurity and duration of respiratory support.ResultsOne hundred and twenty-one randomised participants (azithromycin: n=60; placebo: n=61) were included in the intent-to-treat analysis (mean gestational age 26.2±1.4 weeks). Forty-four of 121 participants (36%) were Ureaplasma positive (azithromycin: n=19; placebo: n=25). Ureaplasma-free survival was 55/60 (92% (95% CI 82% to 97%)) for azithromycin compared with 37/61 (61% (95% CI 48% to 73%)) for placebo. Mortality was similar comparing the two treatment groups (5/60 (8%) vs 6/61 (10%)). Azithromycin effectively eradicated Ureaplasma in all azithromycin-assigned colonised infants, but 21/25 (84%) Ureaplasma-colonised participants receiving placebo were culture positive at one or more follow-up timepoints. Most of the neonatal mortality and morbidity was concentrated in 21 infants with lower respiratory tract Ureaplasma colonisation. In a subgroup analysis, physiological BPD-free survival was 5/10 (50%) (95% CI 19% to 81%) among azithromycin-assigned infants with lower respiratory tract Ureaplasma colonisation versus 2/11 (18%) (95% CI 2% to 52%) in placebo-treated infants.ConclusionA 3-day azithromycin regimen effectively eradicated respiratory tract Ureaplasma colonisation in this study.Trial registration numberNCT01778634.
| S-EPMC7592356 | biostudies-literature
Project description:Lactobacillus reuteri DSM 17938 supplementation reduces morbidities in very low birth weight infants (<1500 g), while the effect on extremely low birth weight infants (ELBW, <1000 g) is still questioned. In a randomised placebo-controlled trial (ClinicalTrials.gov ID NCT01603368), head growth, but not feeding tolerance or morbidities, improved in L. reuteri-supplemented preterm ELBW infants. Here, we investigate colonisation with the probiotic strain in preterm ELBW infants who received L. reuteri DSM 17938 or a placebo from birth to postmenstrual week (PMW) 36. Quantitative PCR was used on 582 faecal DNA samples collected from 132 ELBW infants at one, two, three, and four weeks, at PMW 36, and at two years of age. Human milk oligosaccharides were measured in 31 milk samples at two weeks postpartum. At least 86% of the ELBW infants in the L. reuteri group were colonised with the probiotic strain during the neonatal period, despite low gestational age, high antibiotic pressure, and independent of infant feeding mode. Higher concentrations of lacto-N-tetraose, sialyl-lacto-N-neotetraose c, and 6'-sialyllactose in mother's milk weakly correlated with lower L. reuteri abundance. Within the L. reuteri group, higher L. reuteri abundance weakly correlated with a shorter time to reach full enteral feeding. Female sex and L. reuteri colonisation improved head growth from birth to four weeks of age. In conclusion, L. reuteri DSM 17938 supplementation leads to successful colonisation in ELBW infants.
| S-EPMC8190634 | biostudies-literature
Project description:ObjectiveDetermine if targeting higher transcutaneous carbon dioxide improves respiratory stability among very preterm infants on ventilatory support.DesignSingle-centre pilot randomised clinical trial.SettingThe University of Alabama at Birmingham.PatientsVery preterm infants on ventilatory support after postnatal day 7.InterventionsInfants were randomised to two different transcutaneous carbon dioxide levels targeting 5 mm Hg (0.67 kPa) changes with four sessions each lasting 24 hours for 96 hours: baseline-increase-baseline-increase or baseline-decrease-baseline-decrease.Main outcome measuresWe collected cardiorespiratory data evaluating episodes of intermittent hypoxaemia (oxygen saturations (SpO2)<85% for ≥10 s), bradycardia (<100 bpm for ≥10 s), and cerebral and abdominal hypoxaemia on near-infrared spectroscopy.ResultsWe enrolled 25 infants with a gestational age of 24 w 6 d±11 d (mean±SD) and birth weight 645±142 g on postnatal day 14±3. Continuous transcutaneous carbon dioxide values (56.8±6.9 in the higher group vs 54.5±7.8 in the lower group; p=0.36) did not differ significantly between groups during the intervention days. There were no differences in intermittent hypoxaemia (126±64 vs 105±61 per 24 hours; p=0.30) or bradycardia (11±16 vs 15±23 per hour; p=0.89) episodes between groups. The proportion of time with SpO2<85%, SpO2<80%, cerebral hypoxaemia or abdominal hypoxaemia did not differ (all p>0.05). There was moderate negative correlation between mean transcutaneous carbon dioxide and bradycardia episodes (r=-0.56; p<0.001).ConclusionTargeting 5 mm Hg (0.67 kPa) changes in transcutaneous carbon dioxide did not improve respiratory stability among very preterm infants on ventilatory support but the intended carbon dioxide separation was difficult to achieve and maintain.Trial registration numberNCT03333161.
| S-EPMC10578058 | biostudies-literature
Project description:ObjectiveTo determine if it is possible to stabilise the cerebral oxygenation of extremely preterm infants monitored by cerebral near infrared spectroscopy (NIRS) oximetry.DesignPhase II randomised, single blinded, parallel clinical trial.SettingEight tertiary neonatal intensive care units in eight European countries.Participants166 extremely preterm infants born before 28 weeks of gestation: 86 were randomised to cerebral NIRS monitoring and 80 to blinded NIRS monitoring. The only exclusion criterion was a decision not to provide life support.InterventionsMonitoring of cerebral oxygenation using NIRS in combination with a dedicated treatment guideline during the first 72 hours of life (experimental) compared with blinded NIRS oxygenation monitoring with standard care (control).Main outcome measuresThe primary outcome measure was the time spent outside the target range of 55-85% for cerebral oxygenation multiplied by the mean absolute deviation, expressed in %hours (burden of hypoxia and hyperoxia). One hour with an oxygenation of 50% gives 5%hours of hypoxia. Secondary outcomes were all cause mortality at term equivalent age and a brain injury score assessed by cerebral ultrasonography.RandomisationAllocation sequence 1:1 with block sizes 4 and 6 in random order concealed for the investigators. The allocation was stratified for gestational age (<26 weeks or ≥ 26 weeks).BlindingCerebral oxygenation measurements were blinded in the control group. All outcome assessors were blinded to group allocation.ResultsThe 86 infants randomised to the NIRS group had a median burden of hypoxia and hyperoxia of 36.1%hours (interquartile range 9.2-79.5%hours) compared with 81.3 (38.5-181.3) %hours in the control group, a reduction of 58% (95% confidence interval 35% to 73%, P<0.001). In the experimental group the median burden of hypoxia was 16.6 (interquartile range 5.4-68.1) %hours, compared with 53.6 (17.4-171.3) %hours in the control group (P=0.0012). The median burden of hyperoxia was similar between the groups: 1.2 (interquartile range 0.3-9.6) %hours in the experimental group compared with 1.1 (0.1-23.4) %hours in the control group (P=0.98). We found no statistically significant differences between the two groups at term corrected age. No severe adverse reactions were associated with the device.ConclusionsCerebral oxygenation was stabilised in extremely preterm infants using a dedicated treatment guideline in combination with cerebral NIRS monitoring.Trial registration ClinicalTrial.gov NCT01590316.
| S-EPMC4283997 | biostudies-literature
Project description:ObjectiveUncertainty exists regarding optimal supplemental diet for very preterm infants if the mother's own milk (MM) is insufficient. We evaluated feasibility for a randomised controlled trial (RCT) powered to detect important differences in health outcomes.MethodsIn this open, parallel, feasibility trial, we randomised infants 25+0-31+6 weeks of gestation by opt-out consent to one of three diets: unfortified human milk (UHM) (unfortified MM and/or unfortified pasteurised human donor milk (DM) supplement), fortified human milk (FHM) (fortified MM and/or fortified DM supplement), and unfortified MM and/or preterm formula (PTF) supplement from birth to 35+0 weeks post menstrual age. Feasibility outcomes included opt-outs, adherence rates, and slow growth safety criteria. We also obtained anthropometry, and magnetic resonance imaging body composition data at term and term plus 6 weeks (opt-in consent).ResultsOf 35 infants randomised to UHM, 34 to FHM, and 34 to PTF groups, 21, 19, and 24 infants completed imaging at term, respectively. Study entry opt-out rate was 38%; 6% of parents subsequently withdrew from feeding intervention. Two infants met predefined slow weight gain thresholds. There were no significant between-group differences in term total adipose tissue volume (mean [SD]: UHM: 0.870 L [0.35 L]; FHM: 0.889 L [0.31 L]; PTF: 0.809 L [0.25 L], p = 0.66), nor in any other body composition measure or anthropometry at either timepoint.ConclusionsRandomisation to UHM, FHM, and PTF diets by opt-out consent was acceptable to parents and clinical teams, associated with safe growth profiles and no significant differences in body composition. Our data provide justification to proceed to a larger RCT.
| S-EPMC10994632 | biostudies-literature
Project description:BACKGROUND:The pivotal role of vitamin D (vit D) in skeletal health is well known. Neonatal vit D storage at birth is dependent on maternal levels, and newborns receive 50-70% of their mother's 25-hydroxyvitamin D [25(OH)D]. Deficiency of vit D can lead to prematurity bone disease, with an incidence of up to 55% in infants weighing?<?1000 g. The aim of this study is to assess the effectiveness of monitored supplementation of vit D in a population of preterm infants. METHODS/DESIGN:Preterm infants born at 24-32 weeks of gestation will be recruited within the first 7 days of life. Depending on the type of feeding, and after reaching partial enteral feeding or at 7 days of life, vit D supplementation will consist of 500 IU and an additional 150-300 IU/kg included in human milk fortifiers (if fed exclusively with breast milk) or 190 IU/kg in milk formulas. Subjects will be randomised to either monitored (with an option of dose modification based on 25(OH)D levels as per protocol) or standard therapy up to 52 weeks of post-conceptional age (PCA). The primary outcome measure will be the number of neonates with deficiency or excess levels of 25(OH)D at 40??±2 weeks of PCA. Additional 25(OH)D levels will be measured at birth, at 4 and 8 weeks of age, and/or at 35 and 52??±2 weeks of PCA. Secondary objectives will include the incidence of osteopenia, nephrocalcinosis and nephrolithiasis. Serum parameters of calcium phosphorus metabolism will also be measured. DISCUSSION:Despite multiple years of research and numerous publications, there is still a lack of consensus in regard to how much vit D infants should receive and how long they should receive it. Because 80% of calcium and phosphorus placental transfer occurs between 24 and 40 weeks of gestation, preterm infants are especially prone to adverse effects of vit D insufficiency. However, both inadequate and excessive amounts of vit D may be unsafe and lead to serious health issues. The results of our study may shed new light on these concerns and contribute to optimising vit D supplementation. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03087149 . Registered on 15 March 2017.
| S-EPMC5594536 | biostudies-literature
Project description:ObjectivesTo determine the effectiveness of corticosteroids in reducing respiratory disorders in infants born at 34-36 weeks' gestation. Design Randomised triple blind clinical trial. Setting A large tertiary teaching hospital in northeast of Brazil. Participants Women at 34-36 weeks of pregnancy at risk of imminent premature delivery. Interventions Betamethasone 12 mg or placebo intramuscularly for two consecutive days. Main outcomes measures Primary outcome was the incidence of respiratory disorders (respiratory distress syndrome and transient tachypnoea of the newborn). Secondary outcomes included the need for ventilatory support, neonatal morbidity, and duration of stay in hospital.Results320 women were randomised, 163 of whom were assigned to the treatment group and 157 to the controls. Final analysis included 143 and 130 infants, respectively. The rate of respiratory distress syndrome was low (two (1.4%) in the corticosteroid group; one (0.8%) in the placebo group; P = 0.54), while the rate of transient tachypnoea was high in both groups (34 (24%) v 29 (22%); P = 0.77). There was no reduction in the risk of respiratory morbidity with corticosteroid use even after adjustment for subgroups of gestational age (34-34(+6) weeks, 35-35(+6) weeks, and ≥ 36 weeks). The adjusted risk of respiratory morbidity was 1.12 (95% confidence interval 0.74 to 1.70). The need for ventilatory support was around 20% in both groups. There was no difference in neonatal morbidity (88 (62%) v 93 (72%); P = 0.08) or in the duration of stay in hospital between the two groups (5.12 v 5.22 days; P = 0.87). Phototherapy for jaundice was required less often in babies whose mothers received corticosteroids (risk ratio 0.63, 0.44 to 0.91).ConclusionsAntenatal treatment with corticosteroids at 34-36 weeks of pregnancy does not reduce the incidence of respiratory disorders in newborn infants. Trial registration Clinical Trials NCT00675246.
| S-EPMC3075234 | biostudies-literature
Project description:ObjectiveTo compare the effect of two different automated oxygen control devices on target range (TR) time and occurrence of hypoxaemic and hyperoxaemic episodes.DesignRandomised cross-over study.SettingTertiary level neonatal unit in the Netherlands.PatientsPreterm infants (n=15) born between 24+0 and 29+6 days of gestation, receiving invasive or non-invasive respiratory support with oxygen saturation (SpO2) TR of 91%-95%. Median gestational age 26 weeks and 4 days (IQR 25 weeks 3 days-27 weeks 6 days) and postnatal age 19 (IQR 17-24) days.InterventionsInspired oxygen concentration was titrated by the OxyGenie controller (SLE6000 ventilator) and the CLiO2 controller (AVEA ventilator) for 24 hours each, in a random sequence, with the respiratory support mode kept constant.Main outcome measuresTime spent within set SpO2 TR (91%-95% with supplemental oxygen and 91%-100% without supplemental oxygen).ResultsTime spent within the SpO2 TR was higher during OxyGenie control (80.2 (72.6-82.4)% vs 68.5 (56.7-79.3)%, p<0.005). Less time was spent above TR while in supplemental oxygen (6.3 (5.1-9.9)% vs 15.9 (11.5-30.7)%, p<0.005) but more time spent below TR during OxyGenie control (14.7 (11.8%-17.2%) vs 9.3 (8.2-12.6)%, p<0.05). There was no significant difference in time with SpO2 <80% (0.5 (0.1-1.0)% vs 0.2 (0.1-0.4)%, p=0.061). Long-lasting SpO2 deviations occurred less frequently during OxyGenie control.ConclusionsThe OxyGenie control algorithm was more effective in keeping the oxygen saturation within TR and preventing hyperoxaemia and equally effective in preventing hypoxaemia (SpO2 <80%), although at the cost of a small increase in mild hypoxaemia.Trial registry numberNCT03877198.
| S-EPMC8685610 | biostudies-literature
Project description:ObjectiveTo test a multifaceted collaborative quality improvement intervention designed to promote evidence based surfactant treatment for preterm infants of 23-29 weeks' gestation.DesignCluster randomised controlled trial.Setting and participants114 neonatal intensive care units (which treated 6039 infants of 23-29 weeks gestation born in 2001).Main outcome measuresProcess of care measures: proportion of infants receiving first surfactant in the delivery room, proportion receiving first surfactant more than two hours after birth, and median time from birth to first dose of surfactant. Clinical outcomes: death before discharge home, and pneumothorax.InterventionMultifaceted collaborative quality improvement advice including audit and feedback, evidence reviews, an interactive training workshop, and ongoing faculty support via conference calls and email.ResultsCompared with those in control hospitals, infants in intervention hospitals were more likely to receive surfactant in the delivery room (adjusted odds ratio 5.38 (95% confidence interval 2.84 to 10.20)), were less likely to receive the first dose more than two hours after birth (adjusted odds ratio 0.35 (0.24 to 0.53)), and received the first dose of surfactant sooner after birth (median of 21 minutes v 78 minutes, P < 0.001). The intervention effect on timing of surfactant was larger for infants born in the participating hospitals than for infants transferred to a participating hospital after birth. There were no significant differences in mortality or pneumothorax.ConclusionA multifaceted intervention including audit and feedback, evidence reviews, quality improvement training, and follow up support changed the behaviour of health professionals and promoted evidence based practice.
| S-EPMC524548 | biostudies-literature