University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• In healthy infants, do two doses of the new attenuated Human Rotavirus Vaccine (HRV) carry a higher risk of intussusception within 31 days compared to two doses of placebo?

Clinical Bottom Lines

1. Efficacy against severe rotavirus gastroenteritis and associated hospitalization was 85% with no apparent increase in rates of intussception or any other serious adverse effects.¹
2. Given the prevention of hospitalizations, lost work time, and physician visits in otherwise healthy U.S. infants; this vaccine would reduce disease burden substantially with minimal side effects and would be an agreeable addition to the vaccine schedule; it is especially palatable as it is an oral vaccine and requires no injection.²
3. Wide use of the vaccine could also prevent deaths due to severe diarrhea and dehydration in otherwise healthy infants in many developing countries around the world.²
4. Rotarix® must also compete with the other new Human Rotavirus vaccine, Rotateq®, made by a competitor drug company, which is also proving to be safe and effective through clinical trials.

Summary of Key Evidence

1. Using a randomized controlled Phase III trial with ~60,000 otherwise healthy infants (average age 8 weeks), the researchers established that the new attenuated Human Rotavirus vaccine carries no significant increased risk of intussusception within 31 days of either dose versus placebo doses. The safety arm of the trial assessed for any significant adverse effects detectable up to 90 days following the 2nd dose.¹
2. Study design was randomized, controlled and double-blinded, contained adequate power to detect a significant difference for risk factor, and accounted for all participants. The system to assess for intussusception or other adverse effects was adequate to detect cases; it included active surveillance of enrolled infants and local health care facilities as well as follow-up visits.
3. Six patients in the HRV group experienced intussusception within 31 days, as opposed to seven patients in the placebo group, with a relative risk of 0.85, therefore conveying a slight protective advantage to HRV.
4. Using a subset of the same patient group, the researchers determined efficacy against severe rotavirus gastroenteritis and associated hospitalization with the new vaccine was 85% compared to placebo (p<0.001). The NNT is 125 patients (1/[(77/8858)-(12/9009)]).1

Additional Comments

• Biological mechanisms in question are the absorption of the oral HRV within the gut and whether this puts the patient at risk for future development of intussusception, a condition of intestinal telescoping and subsequent edema and possible incarceration.
• Instituting a broad clinical directive to add HRV to the already busy standard immunization schedule recommended for U.S. children obviously involves many different aspects of health care included cost benefit, risk of illness vs. risk of HRV, societal perception of rotavirus, and availability of safe, large scale vaccine production.
  

Citation

1. Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, et al. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med 2006; 354:11-22.

2. Lee BP, Azimi PH, Staat MA, et al. Nonmedical costs associated with rotavirus disease requiring hospitalization. Pediatr Inf Dis J 2005; 24:984-8.
   

CAT Author: Melissa Pike, MD

CAT Appraisers: John Frohna, MD

Date appraised: February 22, 2006