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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: November 10, 2014
Last verified: November 2014
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  
Number of Participants  
[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  
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  
[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.



  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 ]

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
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Time Frame Participants in this study were followed for all serious adverse events (SAEs) and other adverse events (AEs), for up to 42 days following each study vaccination
Additional Description Participants listed in SAE tables (34904–RotaTeq; 34862-Placebo) are those who received study treatment. Other AEs were reported for a pre-defined subset who received ≥1 dose (4808-RotaTeq; 4796–Placebo). Although a participant may have had ≥ 2 AEs they are counted only once in a category. The same participant may appear in different categories.

Frequency Threshold
Threshold above which other adverse events are reported   1%  

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.

The Not Completed total includes participants discontinued at any time before the completion of the third study vaccination and/or the 42-day safety follow-up period post vaccination 3.

Placebo

Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.

The Not Completed total includes participants discontinued at any time before the completion of the third study vaccination and/or the 42-day safety follow-up period post vaccination 3.


Other Adverse Events
    RotaTeq™     Placebo  
Total, other (not including serious) adverse events      
# participants affected / at risk     4000/4800     4047/4787  
Eye disorders      
Conjunctivitis † 1    
# participants affected / at risk     315/4800 (6.56%)     339/4787 (7.08%)  
Gastrointestinal disorders      
Abdominal pain upper † 1    
# participants affected / at risk     53/4800 (1.10%)     40/4787 (0.84%)  
Constipation † 1    
# participants affected / at risk     188/4800 (3.92%)     214/4787 (4.47%)  
Diarrhoea † 1    
# participants affected / at risk     1047/4800 (21.81%)     1022/4787 (21.35%)  
Flatulence † 1    
# participants affected / at risk     273/4800 (5.69%)     282/4787 (5.89%)  
Gastrooesophageal reflux disease † 1    
# participants affected / at risk     62/4800 (1.29%)     59/4787 (1.23%)  
Infantile colic † 1    
# participants affected / at risk     70/4800 (1.46%)     65/4787 (1.36%)  
Regurgitation of food † 1    
# participants affected / at risk     175/4800 (3.65%)     183/4787 (3.82%)  
Teething † 1    
# participants affected / at risk     196/4800 (4.08%)     165/4787 (3.45%)  
Vomiting † 1    
# participants affected / at risk     613/4800 (12.77%)     644/4787 (13.45%)  
General disorders      
Injection site pain † 1    
# participants affected / at risk     216/4800 (4.50%)     228/4787 (4.76%)  
Irritability † 1    
# participants affected / at risk     881/4800 (18.35%)     862/4787 (18.01%)  
Pyrexia † 1    
# participants affected / at risk     1970/4800 (41.04%)     2056/4787 (42.95%)  
Infections and infestations      
Bronchiolitis † 1    
# participants affected / at risk     200/4800 (4.17%)     185/4787 (3.86%)  
Bronchitis † 1    
# participants affected / at risk     79/4800 (1.65%)     73/4787 (1.52%)  
Candida nappy rash † 1    
# participants affected / at risk     46/4800 (0.96%)     51/4787 (1.07%)  
Ear infection † 1    
# participants affected / at risk     94/4800 (1.96%)     107/4787 (2.24%)  
Gastroenteritis † 1    
# participants affected / at risk     447/4800 (9.31%)     454/4787 (9.48%)  
Influenza † 1    
# participants affected / at risk     89/4800 (1.85%)     72/4787 (1.50%)  
Nasopharyngitis † 1    
# participants affected / at risk     276/4800 (5.75%)     277/4787 (5.79%)  
Oral candidiasis † 1    
# participants affected / at risk     185/4800 (3.85%)     188/4787 (3.93%)  
Otitis media † 1    
# participants affected / at risk     624/4800 (13.00%)     602/4787 (12.58%)  
Pharyngitis † 1    
# participants affected / at risk     60/4800 (1.25%)     57/4787 (1.19%)  
Respiratory tract infection † 1    
# participants affected / at risk     97/4800 (2.02%)     83/4787 (1.73%)  
Rhinitis † 1    
# participants affected / at risk     348/4800 (7.25%)     337/4787 (7.04%)  
Upper respiratory tract infection † 1    
# participants affected / at risk     1230/4800 (25.63%)     1279/4787 (26.72%)  
Viral infection † 1    
# participants affected / at risk     105/4800 (2.19%)     121/4787 (2.53%)  
Metabolism and nutrition disorders      
Decreased appetite † 1    
# participants affected / at risk     68/4800 (1.42%)     67/4787 (1.40%)  
Musculoskeletal and connective tissue disorders      
Pain in extremity † 1    
# participants affected / at risk     45/4800 (0.94%)     46/4787 (0.96%)  
Psychiatric disorders      
Agitation † 1    
# participants affected / at risk     215/4800 (4.48%)     180/4787 (3.76%)  
Crying † 1    
# participants affected / at risk     160/4800 (3.33%)     190/4787 (3.97%)  
Restlessness † 1    
# participants affected / at risk     63/4800 (1.31%)     69/4787 (1.44%)  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     471/4800 (9.81%)     456/4787 (9.53%)  
Nasal congestion † 1    
# participants affected / at risk     293/4800 (6.10%)     294/4787 (6.14%)  
Rhinorrhoea † 1    
# participants affected / at risk     222/4800 (4.63%)     254/4787 (5.31%)  
Wheezing † 1    
# participants affected / at risk     52/4800 (1.08%)     51/4787 (1.07%)  
Skin and subcutaneous tissue disorders      
Dermatitis † 1    
# participants affected / at risk     47/4800 (0.98%)     25/4787 (0.52%)  
Dermatitis diaper † 1    
# participants affected / at risk     106/4800 (2.21%)     120/4787 (2.51%)  
Eczema † 1    
# participants affected / at risk     129/4800 (2.69%)     110/4787 (2.30%)  
Rash † 1    
# participants affected / at risk     167/4800 (3.48%)     153/4787 (3.20%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (8.1)



  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
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372


Publications of Results:
Publications automatically indexed to this study:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00090233     History of Changes
Other Study ID Numbers: V260-006, 2004_012
Study First Received: August 25, 2004
Results First Received: June 29, 2009
Last Updated: November 10, 2014
Health Authority: United States: Food and Drug Administration