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Rotavirus Efficacy and Safety Trial (REST)(V260-006)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00090233
First received: August 25, 2004
Last updated: September 18, 2015
Last verified: September 2015
Results First Received: June 29, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Condition: Rotavirus Infections
Interventions: Biological: Rotateq™
Biological: Comparator: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited at 356 sites in Belgium, Costa Rica, Finland, Germany, Guatemala, Italy, Jamaica, Mexico, Puerto Rico, Sweden, Taiwan, and the United States from 12 Jan 2001 first patient in (FPI) to 06 Oct 2004 last patient in (LPI).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Participants with: history of congenital abdominal disorders, intussusception, or abdominal surgery; history of

known prior rotavirus disease, chronic diarrhea, or failure to thrive were excluded from the trial before

assignment to groups.


Reporting Groups
  Description
RotaTeq™ Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart with up to 42 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) through the first rotavirus season postvaccination. The rotavirus season for each site was prospectively determined using historical epidemiologic data.
Placebo Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart with up to 42 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) through the first rotavirus season postvaccination. The rotavirus season for each site was prospectively determined using historical epidemiologic data.

Participant Flow:   Overall Study
    RotaTeq™   Placebo
STARTED   34644 [1]   34630 [2] 
Vaccinated at Visit 1   34035 [3]   34003 [4] 
Vaccinated at Visit 2   31052   31066 
Vaccinated at Visit 3   29667   29598 
COMPLETED   29645 [5]   29565 [5] 
NOT COMPLETED   4999   5065 
Randomized Not Vaccinated (Visit 1)                609                627 
Adverse Event                214                198 
Lost to Follow-up                68                95 
Protocol Violation                960                1022 
Withdrawal by Subject                182                211 
Moved                203                189 
Not Specified                1211                1160 
Data not available at data cut-off point                1552                1563 
[1] Evaluated by data safety monitoring board (DSMB) when they recommended stopping enrollment
[2] Evaluated by data safety monitoring board when they recommended stopping enrollment
[3] Randomized Not vaccinated 609
[4] Randomized Not vaccinated 627
[5] Does not include participants who discontinued prior to the 42 day safety follow-up



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
RotaTeq™ Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
Placebo Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
Total Total of all reporting groups

Baseline Measures
   RotaTeq™   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 34644   34630   69274 
Age, Customized [1] 
[Units: Participants]
     
5 Weeks of Age and Under   1   4   5 
6 to 12 Weeks of Age   34551   34527   69078 
Over 12 Weeks of Age   92   99   191 
[1] The eligibility for this study was to enroll infants 6-12 weeks of age; however infants that were 5 weeks and under, and infants who were 12 weeks and over were inadvertently enrolled outside these ranges. Those infants who received at least 1 dose of study vaccine, were followed for safety.
Gender 
[Units: Participants]
     
Female   17058   17101   34159 
Male   17586   17529   35115 
Race/Ethnicity 
[Units: Participants]
     
White   23772   23788   47560 
Hispanic American   4963   4911   9874 
Black   2908   2941   5849 
Multi Racial   1815   1817   3632 
Asian   536   552   1088 
Native American   531   514   1045 
Other   119   107   226 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Intussusception Within 42 Days Following Any Dose of RotaTeq™/Placebo   [ Time Frame: Within 42 days following any dose of RotaTeq™/placebo ]

2.  Primary:   Occurrence of Rotavirus Disease Caused by Serotypes G1, G2, G3 and G4 That Occurs 14 Days Following the 3rd Vaccination   [ Time Frame: At least 14 days following the 3rd vaccination through the first full rotavirus season ]

3.  Secondary:   G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus   [ Time Frame: 14 days following the 3rd vaccination ]

4.  Secondary:   Occurrence of Hospital Admissions and Visits to Emergency Departments (or the Equivalent at International Sites) for Rotavirus Disease Associated With Serotypes G1, G2, G3, or G4   [ Time Frame: At least 14 days following the 3rd vaccination ]

5.  Secondary:   Efficacy of a 3-dose Regimen of RotaTeq™ Against Moderate-to-severe Rotavirus Disease (Clinical Score >8) Caused by Serotypes G1, G2, G3, and G4 Occurring at Least 14 Days Following the Third Dose.   [ Time Frame: At least 14 days following the 3rd vaccination through the first rotavirus season ]

6.  Secondary:   Efficacy of a 3-dose Regimen of RotaTeq™ Against Severe Rotavirus Disease (Clinical Score > 16) Caused by Serotypes G1, G2, G3, and G4 Occurring at Least 14 Days Following the Third Dose   [ Time Frame: At least 14 days following the 3rd vaccination through the first rotavirus season ]

7.  Secondary:   Seroprotection/Seroconversion for Hepatitis B, Haemophilus Influenzae Type b, Diphtheria, Tetanus, & Polio Types 1,2,& 3 Who Received COMVAX™, INFANRIX™, IPOL™ & PREVNAR™ Concomitantly With RotaTeq™ Versus Placebo   [ Time Frame: 42 days following third dose ]

8.  Secondary:   Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin   [ Time Frame: 42 days following third dose ]
  Hide Outcome Measure 8

Measure Type Secondary
Measure Title Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin
Measure Description Measurement of immune response in the group that received RotaTeq™ and the group that received placebo was performed by determining geometric mean antibody titers to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin. Antibody titers were measured with an indirect, non-competitive, enzyme immunoassay (EIA).
Time Frame 42 days following third dose  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol Population; excluding protocol violators and participants with invalid data based on laboratory determinations.

Reporting Groups
  Description
RotaTeq™ Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
Placebo Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.

Measured Values
   RotaTeq™   Placebo 
Participants Analyzed 
[Units: Participants]
 59   78 
Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin 
[Units: ELISA units/mL]
Geometric Mean (95% Confidence Interval)
   
Pertussis PT   20.18 
 (17.10 to 23.81) 
 22.73 
 (19.59 to 26.37) 
Pertussis FHA   55.69 
 (48.01 to 64.59) 
 64.33 
 (55.41 to 74.69) 
Pertussis Pertactin   34.77 
 (26.46 to 45.70) 
 59.17 
 (46.21 to 75.76) 


Statistical Analysis 1 for Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] <0.001
GMTR for Pertussis PT [5] 0.9
95% Confidence Interval 0.7 to 1.1
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for Pertussis PT was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] <0.001
GMTR for Pertussis FHA [5] 0.9
95% Confidence Interval 0.7 to 1.1
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for Pertussis FHA was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] t-test, 1 sided
P Value [4] 0.193
GMTR for Pertussis Pertactin [5] 0.6
95% Confidence Interval 0.4 to 0.8
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The GMT Ratio between RotaTeq™ and Placebo (GMTR) for Pertussis Pertactin was used for analysis.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  GMTR was greater than 0.5 (non-inferiority margin).
[3] Other relevant method information, such as adjustments or degrees of freedom:
  t-test on natural log of titers
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.



9.  Secondary:   Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F   [ Time Frame: 42 days following third dose ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
70,301 participants randomized, 69,274 evaluated, when DSMB first recommended ending enrollment.


  More Information