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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00090233

Recruitment Status : Completed

First Posted : August 27, 2004

Results First Posted : May 5, 2011

Last Update Posted : October 5, 2015

Sponsor:

Information provided by (Responsible Party):

Merck Sharp & Dohme Corp.

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
Condition:	Rotavirus Infections
Interventions:	Biological: Rotateq™ Biological: Comparator: Placebo

Participant Flow

Hide Participant Flow

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.

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.

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

Hide Baseline Characteristics

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

6 to 12 Weeks of Age

34551

34527

69078

Over 12 Weeks of Age

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 ]

Show Outcome Measure 1

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 ]

Show Outcome Measure 2

3. Secondary:

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

Hide Outcome Measure 3

Measure Type	Secondary
Measure Title	G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus
Measure Description	Number of participants with a 3-fold rise or greater in G1 Serum neutralizing antibody (SNA) responses against rotavirus from baseline to postdose 3.
Time Frame	14 days following the 3rd vaccination

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 among participants in Finland using Per-Protocol Case Definition

Reporting Groups

	Description
RotaTeq™	Participants randomized to treatment with RotaTeq™ tested with data available for analysis excluding protocol violators, participants with invalid data based on laboratory determinations, participants with wildtype rotavirus detected in the stool, or with samples taken outside the range of 9 to 33 days postdose 3.
Placebo	Participants randomized to treatment with Placebo tested with data available for analysis excluding protocol violators, participants with invalid data based on laboratory determinations, participants with wildtype rotavirus detected in the stool, or with samples taken outside the range of 9 to 33 days postdose 3.

Measured Values

	RotaTeq™	Placebo
Participants Analyzed [Units: Participants]	117	89
G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus [Units: Participants]	95	8

Statistical Analysis 1 for G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus

Groups ^[1]	RotaTeq™
Statistical Test Type ^[2]	Superiority or Other
Statistical Method ^[3]	Exact binomial test
P Value ^[4]	<0.001
Proportion ^[5]	81.2
95% Confidence Interval	72.9 to 87.8

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	No text entered.
[3]	Other relevant method information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	p≥42%, where p is proportion of participants with ≥3-fold rise in antibody titer from Predose 1 to Postdose 3 in vaccine group. Based on binomial approach.
[5]	Other relevant estimation information:
	No text entered.

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 ]

Show Outcome Measure 4

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 ]

Show Outcome Measure 5

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 ]

Show Outcome Measure 6

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 ]

Show Outcome Measure 7

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 ]

Show Outcome Measure 8

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 ]

Show Outcome Measure 9

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

Limitations and Caveats

Hide Limitations and Caveats

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

Show More Information

To Top