title: Neonatal Ventilation With Inhaled Nitric Oxide Versus Ventilatory Support Without Inhaled Nitric Oxide for Preterm Infants With Severe Respiratory Failure: the INNOVO multicentre randomised controlled trial (ISRCTN 17821339).
abstract: BACKGROUND
  Although inhaled nitric oxide (iNO) may be a promising treatment for newborn infants with severe respiratory failure, the results from 3 previous small trials were inconclusive.
  
  
  METHODS
  Infants of <34 weeks' gestation, <28 days old, and with severe respiratory failure requiring ventilatory support were randomized to receive or not receive iNO. The study was not blinded.
  
  
  RESULTS
  Recruited were 108 infants (55 allocated to receive iNO and 53 not allocated to receive iNO) from 15 neonatal units in the United Kingdom and Republic of Ireland. Fifty-nine percent (64 of 108) died, and 84% of the survivors (37 of 44) had signs of some impairment or disability, 9 (20%) of them classified as severely disabled. There was no evidence of an effect of iNO on the primary outcomes: death or severe disability at 1 year corrected age (relative risk [RR]: 0.99; 95% confidence interval [CI]: 0.76 to 1.29); death or supplemental oxygen on expected date of delivery (RR: 0.84; 95% CI: 0.68 to 1.02); or death or supplemental oxygen at 36 weeks' postmenstrual age (RR: 0.98; 95% CI: 0.87 to 1.12). There was a trend for infants allocated to the iNO group to spend more time on the ventilator (log rank: 3.6), on supplemental oxygen (log rank: 1.4), and in hospital (log rank: 3.5) than those allocated to receive no iNO. This pattern predominantly reflected the infants who died. Mean total costs at 1 year corrected age were significantly higher in the iNO group, partly because of the costs of the gas but mainly because of the difference in initial hospitalization costs.
  
  
  CONCLUSIONS
  Evidence of prolongation of intensive care and increased costs of such care, without clear beneficial effects, implies that iNO cannot be recommended for preterm infants with severe hypoxic respiratory failure.
authors.affiliation: Department of Health Science, Leicester Royal Infirmary, PO Box 65, Leicester LE2 7LX, United Kingdom. david.field@uhl-tr.nhs.uk
authors.forename: D
authors.initials: D
authors.lastname: Field
authors.forename: D
authors.initials: D
authors.lastname: Elbourne
authors.forename: A
authors.initials: A
authors.lastname: Truesdale
authors.forename: R
authors.initials: R
authors.lastname: Grieve
authors.forename: P
authors.initials: P
authors.lastname: Hardy
authors.forename: A C
authors.initials: AC
authors.lastname: Fenton
authors.forename: N
authors.initials: N
authors.lastname: Subhedar
authors.forename: J
authors.initials: J
authors.lastname: Ahluwalia
authors.forename: H L
authors.initials: HL
authors.lastname: Halliday
authors.forename: J
authors.initials: J
authors.lastname: Stocks
authors.forename: K
authors.initials: K
authors.lastname: Tomlin
authors.forename: C
authors.initials: C
authors.lastname: Normand
mesh_terms: D000280:Administration, Inhalation; D003131:Combined Modality Therapy; D002658:Developmental Disabilities / Q000453:epidemiology; D019988:Children with Disabilities; D005260:Female; D017048:Health Care Costs; D006295:Health Resources / Q000706:statistics & numerical data; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000401:mortality / Q000628:therapy*; D007902:Length of Stay; D008171:Lung Diseases / Q000453:epidemiology; D008297:Male; D009569:Nitric Oxide / Q000191:economics / Q000627:therapeutic use*; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000150:complications / Q000401:mortality / Q000628:therapy*; D017211:Treatment Failure
chemical_list: D009569:Nitric Oxide