Objective: To study the safety, immunogenicity, and protective efficacy of the Haemophilus influenzae capsular polysaccharide tetanus conjugate vaccine (PRP-T).
Design: Randomized, double-blind, controlled clinical trial.
Setting: Southern California Kaiser-Permanente Health Plan.
Participants: 10,317 infants 6 to 15 weeks of age, with no known immune dysfunction, exposure to hepatitis B, or contraindication to diphtheria-tetanus-pertussis (DTP) vaccination were enrolled between August 1989 and September 1990.
Intervention: Infants were randomized to receive either PRP-T or a recombinant hepatitis B control vaccine (in addition to DTP) at approximately 2, 4, and 6 months of age.
Outcome measures: Adverse reactions occurring during the first 72 hours and between doses (including hospitalizations and outpatient visits) were measured using parental reporting/interviews and review of records. Invasive disease caused by H influenzae was ascertained from the time of enrollment until December 31, 1990.
Results: In October 1990, the study was prematurely terminated because of licensure of other H influenzae vaccines recommended for routine infant use. The rates of systemic and local reactions occurring within 72 hours of each vaccine dose were generally similar for infants given PRP-T and hepatitis B, but some reaction rates (local reactions, fever > or = 102 degrees F, irritability, crying) were significantly higher in the PRP-T group. In the month following receipt of vaccine, PRP-T-vaccinated infants experienced five definite seizures compared with three in the hepatitis B control group. Within 48 hours of vaccination, three seizures (two definite and one possible), which were thought to be related to vaccination, occurred in the PRP-T group, compared with none in the control group (P < .13). Overall morbidity, mortality, and hospitalization rates were similar in the two vaccine groups. Three cases of invasive disease caused by H influenzae occurred in the control group; none occurred in the PRP-T group.
Conclusions: The PRP-T vaccine is safe and appears to be effective in preventing invasive disease caused by H influenzae type b.