Methods

Design: randomised controlled trial
Method of randomisation: random patient numbers generated before entry of patients
Means of allocation concealment: randomised code concealed
Blinding: double‐blind, placebo‐controlled
Withdrawal/dropouts: none

Participants

Eligible: 35
Randomised: 17 IVIG: 18 placebo
Completed:17 IVIG: 18 placebo
Inclusion criteria: admitted for treatment of pneumonia or bronchiolitis, weighed 10 kg or less, had nasal swab RSV detected, had parental informed consent
Exclusion Criteria: congenital heart disease, inability to establish IV line, failure to obtain consent, previously known hypersensitivity to blood products

Interventions

Setting: Children's Hospital National Medical Center, Washington DC
Interventions: 2 g of drug (IVIG or albumin placebo) per kg body weight administered over 12 to 24 hours IV

Outcomes

Oximetry reading, RSV titres and clinical statuses daily; 6 week post discharge assessment of general health status plus blood sampling

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

Design: randomised controlled trial
Method of randomisation: not disclosed
Means of allocation concealment: not disclosed
Blinding: not disclosed
Withdrawal/dropouts:three patients ‐ one was eight months with no underlying disease so should not have qualified, two received only half doses of immunoglobulin as they did not tolerate it.

Participants

Eligible: 68
Randomised: 32 IG‐aerosol group/ 33 placebo group
Completed:32 IG‐aerosol/ 33 placebo
Inclusion criteria: at high risk of severe illness: 6 months or younger without underlying disease and 12 months or younger with either underlying diseases or a history of prematurity
Exclusion criteria: administration of ribavirin at the referring hospital before admission to a paediatric centre, administration of systemic or topical steroids before study entrance, previous immunoglobulin therapy, previous reaction to a blood product, and minor symptoms of URTI allowing discharge home from the emergency room the same day

Interventions

Setting: University Children's Hospital, Berne (n = 32), Children's Hospital, Lucerne (n = 16); Children's Hospital, Bienne (n = 11), University Children's Hospital, Zurich (n = 7); and Department of Pediatrics, Kantonsspital, Aarau (n = 2), Switzerland
Interventions: two x 20 min inhalations of 0.05 g/kg body weight IG‐aerosol (Sandoglobulin) 30 to 60 min apart or placebo of 0.05% albumin solution, administered via a nebuliser connected to a modified bag‐mask. The drug was aerosolised at a rate of 4 to 6 L/min. Oxygen was adjusted to maintain saturation above 92%. Spontaneous ventilation was assisted by synchronous hand bag ventilation, for better intrapulmonary drug distribution

Outcomes

Clinical assessment and scoring: severity of illness before and after therapy via a numeric clinical score (0 to 12 points) described by Bierman and Pierson. It is semi‐quantitative on 4 clinical signs: respiratory rate, presence of rales, rhonchi or wheezing demonstrated on auscultation, presence of cyanosis, presence of subcostal or subphrenic recessions. Chest roenterograms scored by a semiquantitative method based on the following criteria: (1) normal lung parenchyma; (2) signs of hyperinflation but normal lung parenchyma; (3) signs of hyperinflation and altered lung parenchyma; and (4) signs or reactive changes to inflammatory stimuli (e.g. hilar lymphadenopathy). Incidence of required intubation, length of hospital stay, duration of oxygen supplementation and frequency of apnoeic spells occurring were reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

B ‐ Unclear

Methods

Design: randomised controlled trial
Method of randomisation: not disclosed
Means of allocation concealment: Massachusetts Public Health Biological Laboratories coded the bottles of RSVIG and placebo so that they were unknown to investigators, sponsor, and study participants
Blinding: double‐blind, placebo controlled
Withdrawals/dropouts: one infant in the RSVIG group who received less than 75% of the infusion, one placebo recipient who had an admission respiratory score of less than 2.5, and one placebo patient on whom an intravenous infusion was unable to be started

Participants

Eligible: 101
Randomised: 47 RSVIG: 54 placebo
Completed: 46 RSVIG: 52 placebo
Inclusion criteria: previously healthy infants and young children, less than or equal to two years of age, hospitalised for bronchiolitis and/or pneumonia with nasal wash specimens positive for RSV antigen by immunofluorescence or enzyme‐linked immunosorbent assay, with acute lower respiratory tract symptoms of less than four days, and had a respiratory score of greater than or equal to 2.5
Exclusion criteria: known or suspected cardiopulmonary disease, premature birth with a gestational age less than 32 weeks, immunodeficiency disease, known serum IgA deficiency, renal failure, or a previous reaction to blood products in the preceding 60 days, an established diagnosis of reactive airways disease, apnoea without evidence of LRTI on presentation, or inability to establish an intravenous line; or if previously given ribavirin therapy

Interventions

Setting: Children's National Medical Center, Washington, DC; The Children's Hospital, Denver, Colorado; Vanderbilt University, Nashville, Tennessee; West Virginia University Health Sciences Center, Morgantown, West Virginia; Albany Medical Center Hospital, Albany, New York.
Interventions: 30 mL/kg (1500 mg/kg) infusion or RSVIG or placebo. The dose of RSVIG was calculated to yield serum neutralizing antibody titres mirroring those achieved in the previous RSV immunoglobulin therapy trial (1:5,000)

Outcomes

Primary endpoint: duration of hospitalisation, defined as the period between the onset of the RSVIG or placebo infusion and the time when the discharge order was written. If the infant's hospitalisation was extended for nonmedical reasons, or for medical reasons not related to the RSV infection (i.e. surgery), the time of discharge was established as the time and date the patient had three consecutive respiratory scores less than 2.0. A reduction in mean hospitalisation days of 20% was considered clinically significant
Secondary endpoints: duration of stay in the intensive care unit (ICU), duration of mechanical ventilation, duration of oxygen therapy, use of ribavirin, and supplemental oxygen. A difference of one day between treatment groups in duration of ICU stay or mechanical ventilation was considered to be clinically significant

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Low risk

A ‐ Adequate

Methods

Design: randomised controlled trial
Method of randomisation: balancing randomisation in blocks of six vials, with three RSVIG and three placebo vials per set of six. The vials were coded with a letter
Means of concealment: the Massachusetts Public Health Biological Laboratories (MPHBL) selected the high titre RSVIG and prepared identical looking vials which contained either the RSVIG or placebo. Only the MPHBL and the Data and Safety Monitoring Board (which lettered the vials) knew the contents of the vials and this was not disclosed until after the study
Blinding: double‐blinding, placebo‐controlled
Withdrawals/dropouts: three children in the RSVIG group and two in the placebo group received less than the stipulated 75% of the ordered dose and thus were not able to be evaluated for efficacy

Participants

Eligible: 107
Randomised: 54 RSVIG/ 53 placebo
Completed: 51 RSVIG/ 51 placebo
Inclusion criteria: severe bronchopulmonary dysplasia (BPD) with an oxygen requirement within 6 months of beginning the study, other serious chronic lung disease with an oxygen requirement for at least 30 days within 6 months of beginning the study, congenital heart disease ‐ either uncorrected or uncorrectable lesions which included: infants with cardiomyopathy and infants with increased flow and/or pulmonary hypertension as documented by cardiac catheterisation or echocardiograms; and preterm infants less than six months old and less than 32 weeks gestation. All patients must have presented with acute lower respiratory illness
Exclusion criteria: poorly controlled congestive heart failure before the RSV illness, renal failure, ventilator dependency before the RSV illness, life expectancy of less than six months before the start of the study, treatment with ribavirin before enrolment to the study, known serum IgA deficiency or other immunodeficiency, and enrollment in another RSVIG RSV prophylaxis study. Also excluded were patients with known cystic fibrosis, asthma, or reactive airway disease in the absence of BPD. Patients presenting with apnoea without any other signs of LRTI were also excluded

Interventions

Setting: Children's National Medical Center, Washington, DC, Children's Hospital, Denver, CO; New England Medical Center, Boston, MA; Vanderbilt University Medical Center, Nashville, TN; Buffalo Children's Hospital, Buffalo, NY; Albany Medical College, Albany, NY; University of Rochester Medical Center, Rochester, NY; Children's Mercy Hospital, Kansas City, MO;West Virginia University Health Sciences Center, Morgantown, WV
Interventions: one 30 ml/kg dose of RSVIG or placebo, administered intravenously in 12 hours. This equated to a dose of 1.5 mg/kg IVIG or 0.15 mg/kg albumin (placebo). It was estimated that this would achieve serum‐neutralising antibody titres approximating those achieved in the previous RSVIG trial (1:5,000)

Outcomes

Respiratory score from zero to five with parameters consisting of relevant measures of RSV disease severity: respiratory rate, oxygen saturation, adventitial sounds, and retractions. An analogue score was also used which was a visual scoring system that measures increment improvement based on a clinical continuous line that represents the total range of possible illness. A chest radiograph was obtained on admission and discharge. Duration of hospitalisation was also an outcome measure

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

D ‐ Not used