Influenza-like IllnessPhase 4NCT03656198

Non-specific Effects of Rabies Vaccine

A Phase 4 study testing Rabivax-S and Sterile Water Injection in people with Influenza-like Illness and Upper Respiratory Disease, run by Ross University School of Veterinary Medicine at 1 site in Saint Kitts and Nevis.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Any ageHealthy volunteers can take part
Conditions the study is for: Influenza-like Illness, Upper Respiratory Disease, Diarrhea
What is being tested?: Rabivax-S and Sterile Water Injection
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 546 participants
Where: 1 siteSaint Kitts and Nevis
Study dates: 29 Aug 2018to 27 Jul 2020
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
Healthy volunteers accepted
Child, Adult, Older adult

Who may be able to join

A student registered at RUSVM, and in the Veterinary Preparatory (VP) program or the 1st or 5th semester of the Doctor of Veterinary Medicine (DVM) program

Who cannot join

A student registered at RUSVM and in the VP program or the 1st or 5th semester of the DVM program will be excluded from the study if s/he:
has previously received a dose of rabies vaccine, or
is intending to undertake activities during the course of participation in the study that would increase their risk category of rabies exposure above that of the U.S. population at large, as defined by the Advisory Committee on Immunization Practices (ACIP) for human rabies prevention, or
does not provide informed consent for participation, or
enrolls in the study but does not present for the first injection within the first 12 weeks of the semester (up to and including Week 12), or
has a contraindication to rabies vaccine as described in the Rabivax-S package insert

Trial locations and contacts

1 site in 1 country.

Saint Kitts and Nevis1 site

Ross University School of Veterinary Medicine
Basseterre

About this study

Official title: Non-specific Effects of Rabies Vaccine on the Incidence of Common Infectious Disease Episodes: a Randomized Controlled Trial

Vaccines work by stimulating the body to produce a high-quality, rapid and specific immune response upon exposure to infection by a particular disease-causing microorganism - the microorganism targeted by the vaccine. Evidence is emerging that some vaccines may have additional 'non-specific effects' (NSEs); that is, effects on the immune system beyond the direct protection against the diseases for which the vaccines were developed. It has been proposed that rabies vaccine has protective NSEs in people and animals, with receipt of rabies vaccine in children associated with a reduced risk of meningitis and cerebral malaria in one study, and a history of rabies vaccination in free-roaming dogs associated with increased survival rates in another study. Studies in mice have shown that prior rabies vaccination protects against bacterial sepsis. The biological mechanism of action of any such NSE of rabies vaccine is unknown. Other vaccines with reported protective NSEs (e.g. bacillus Calmette-Guerin vaccine against tuberculosis, a disease caused by Mycobacterium tuberculosis) have been show to reprogram the immune system, leading to enhanced protection against infection with disease-causing microorganisms unrelated to M. tuberculosis.

In this study, we will test the hypothesis that rabies vaccine has non-specific protective effects against common infectious disease (CID) syndromes (upper respiratory illness, diarrhea and fever) in a population of veterinary students. We will randomly assign previously-unvaccinated students who volunteer for the study to receive a primary course of three injections of rabies vaccine (experimental group) or an identical course of three injections of sterile water (control group). Participants will not know to which group they have been assigned. We will ask all participants to report episodes of illness through an online survey each week for 26 weeks, and will also record all clinically- and laboratory-confirmed cases of illness with CID syndromes. We hypothesize that rates of self-reported new episodes of CID illness over 26 weeks will be at least 25% lower in the experimental group, relative to the control group.

Conditions: Influenza-like Illness, Upper Respiratory Disease, Diarrhea, Fever
Being tested: Rabivax-S, Sterile Water Injection
Keywords: Non-Specific Effects of Vaccines, Heterologous Immunity, Rabies, Patient Reported Outcome Measures
Medical subject headings: Respiration Disorders, Diarrhea, Fever, Rabies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Rabivax-SBiological
Rabivax-S is a lyophilized vaccine manufactured by Serum Institute of India Pvt. Ltd. containing inactivated purified rabies antigen (Pitman Moore, PM3218 as virus strain) produced using Vero ATCC CCL 81 cells. The diluent (sterile water for injection) is provided in a separate 1 mL ampoule. After reconstitution, a single dose of 1 mL contains an inactivated, purified rabies antigen (not less than 2.5 IU), glycine (40 mg), sucrose (40 mg) and human serum albumin (25% 10 mg).
Sterile Water InjectionDrug
The vaccine diluent (sterile water for injection) is provided in a separate 1 mL ampoule.

Study groups in NCT03656198
Study group	Role	What they receive
Vaccine group	Experimental	Three dose primary course of Rabivax-S. Dosing and administration of the vaccine (Rabivax-S) will be according to the package insert, following the schedule for pre-exposure prophylaxis via the intramuscular route; that is, 1 mL by intramuscular injection in the deltoid area of the arm on Day 0, Day 7 and Day 21. Receives: Biological: Rabivax-S
Control group	Placebo comparator	The intervention (placebo) in the control group is at least one dose (1 mL by intramuscular injection) of a three dose primary course (on days 0, 7 and 21) of vaccine diluent (sterile water for injection). Receives: Drug: Sterile Water Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of self-reported new episodes of acute common infectious disease (CID), defined as any of the following: upper respiratory illness (URI) or influenza-like illness (ILI) or diarrhea (DIA) or undifferentiated febrile illness (UFI)
URI is defined as (two or more of the following: runny or blocked nose/sneezing/sore throat/cough) and (absence of itchy or watery eyes).
ILI is defined as [fever (feeling feverish, or an axillary, oral or otic temperature of 100°F or higher)] and (cough or sore throat).
DIA is defined as three or more loose stools within a 24-hour period.
UFI is defined as [fever (feeling feverish, or an axillary, oral or otic temperature of 100°F or higher)] and (not meeting the case definition of URI, ILI or DIA).
To be defined as a new episode, illness must be preceded by at least one week without any CID.
Measured: Weekly self-reporting of occurrence or non-occurrence of episodes of CID for a maximum of 26 weeks, starting one week after allocation

Secondary outcomes (7)

Number of self-reported new episodes of respiratory illness (URI or ILI), DIA and UFI
Measured: Weekly self-reporting of occurrence or non-occurrence of episodes of respiratory illness, DIA and UFI for a maximum of 26 weeks, starting one week after allocation
Number of self-reported new weekly episodes of URI
To be defined as a new episode, illness must be preceded by at least one week without any URI.
Measured: Weekly self-reporting of occurrence or non-occurrence of episodes of URI for a maximum of 26 weeks, starting one week after allocation
Number of self-reported new weekly episodes of ILI
To be defined as a new episode, illness must be preceded by at least one week without any ILI.
Measured: Weekly self-reporting of occurrence or non-occurrence of episodes of ILI for a maximum of 26 weeks, starting one week after allocation
Number of self-reported new weekly episodes of DIA
To be defined as a new episode, illness must be preceded by at least one week without any DIA.
Measured: Weekly self-reporting of occurrence or non-occurrence of episodes of DIA for a maximum of 26 weeks, starting one week after allocation
Number of self-reported new weekly episodes of UFI
To be defined as a new episode, illness must be preceded by at least one week without any UFI.
Measured: Weekly self-reporting of occurrence or non-occurrence of episodes of UFI for a maximum of 26 weeks, starting one week after allocation
Number of clinically-confirmed episodes of CID syndromes
Clinically-confirmed episodes of CID syndromes, defined as an episode resulting in a visit to the RUSVM Student Health Services with a recorded ICD10 of J00 (acute nasopharyngitis); J11 (influenza due to unidentified influenza virus); R19.7 (diarrhea) or R50.9 (fever, unspecified).
Measured: 27 weeks after allocation
Number of laboratory-confirmed episodes of CID syndromes
Laboratory-confirmed episodes of CID syndromes, defined as clinically-confirmed episodes with laboratory diagnosis of influenza virus, respiratory syncytial virus or metapneumovirus (URI/ILI episodes) or rotavirus or norovirus (DIA episodes)
Measured: 27 weeks after allocation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

29 Aug 201827 Jul 2020

First posted4 Sep 2018
Study start29 Aug 2018
Primary completion27 Jul 2020
Study completion27 Jul 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Influenza-like IllnessStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Model description: The trial design is a single-site, two-arm, parallel-group, participant-blinded, randomized, placebo-controlled, two-sided comparative study, with an internal pilot study for blinded sample size re-estimation. Allocation to study arm will be by block randomization stratified by sex within cohort (semester) with a 1:1 allocation ratio.
Masking: Single blind
Who is masked: Participant
Enrolment: 546 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03656198
Sponsor's protocol ID: 18-04-FL
Status last verified: Aug 2021
First submitted: 24 Aug 2018
Last updated: 13 Aug 2021
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Odita CI, Conan A, Smith-Antony M, Battice J, England S, Barry D, Gessner BD, Knobel DL. Non-specific effects of rabies vaccine on the incidence of self-reported common infectious disease episodes: A randomized controlled trial. Vaccine. 2022 Mar 8;40(11):1617-1623. doi: 10.1016/j.vaccine.2021.06.007. Epub 2021 Jun 11.
PubMed 34127294
Knobel D, Odita CI, Conan A, Barry D, Smith-Anthony M, Battice J, England S, Gessner BD. Non-specific effects of rabies vaccine on the incidence of common infectious disease episodes: study protocol for a randomized controlled trial. Trials. 2020 Jun 16;21(1):534. doi: 10.1186/s13063-020-04467-z.
PubMed 32546199

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 13 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Non-specific Effects of Rabies Vaccine on the Incidence of Common Infectious Disease Episodes: a Randomized Controlled Trial
ClinicalTrials.gov ID: NCT03656198
Acronym / sponsor ID: 18-04-FL
Conditions: Influenza-like Illness, Upper Respiratory Disease, Diarrhea, Fever
Keywords: Non-Specific Effects of Vaccines, Heterologous Immunity, Rabies, Patient Reported Outcome Measures
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 546 participants (actual)
Lead sponsor: Ross University School of Veterinary MedicineUniversity, hospital or other
Collaborators: Serum Institute of India Pvt. Ltd.
Study start: 29 Aug 2018 (actual)
Primary completion: 27 Jul 2020 (actual)
Study completion: 27 Jul 2020 (actual)
First posted: 4 Sep 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 2
Model description: The trial design is a single-site, two-arm, parallel-group, participant-blinded, randomized, placebo-controlled, two-sided comparative study, with an internal pilot study for blinded sample size re-estimation. Allocation to study arm will be by block randomization stratified by sex within cohort (semester) with a 1:1 allocation ratio.

Arm	Type	Receives
Vaccine group	Experimental	Biological: Rabivax-SThree dose primary course of Rabivax-S. Dosing and administration of the vaccine (Rabivax-S) will be according to the package insert, following the schedule for pre-exposure prophylaxis via the intramuscular route; that is, 1 mL by intramuscular injection in the deltoid area of the arm on Day 0, Day 7 and Day 21.
Control group	Placebo comparator	Drug: Sterile Water InjectionThe intervention (placebo) in the control group is at least one dose (1 mL by intramuscular injection) of a three dose primary course (on days 0, 7 and 21) of vaccine diluent (sterile water for injection).

Who may qualify

Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (1 listed)

A student registered at RUSVM, and in the Veterinary Preparatory (VP) program or the 1st or 5th semester of the Doctor of Veterinary Medicine (DVM) program

Key exclusion criteria (6 listed)

A student registered at RUSVM and in the VP program or the 1st or 5th semester of the DVM program will be excluded from the study if s/he:
has previously received a dose of rabies vaccine, or
is intending to undertake activities during the course of participation in the study that would increase their risk category of rabies exposure above that of the U.S. population at large, as defined by the Advisory Committee on Immunization Practices (ACIP) for human rabies prevention, or
does not provide informed consent for participation, or
enrolls in the study but does not present for the first injection within the first 12 weeks of the semester (up to and including Week 12), or

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Rabivax-SRabivax-S is a lyophilized vaccine manufactured by Serum Institute of India Pvt. Ltd. containing inactivated purified rabies antigen (Pitman Moore, PM3218 as virus strain) produced using Vero ATCC CCL 81 cells. The diluent (sterile water for injection) is provided in a separate 1 mL ampoule. After reconstitution, a single dose of 1 mL contains an inactivated, purified rabies antigen (not less than 2.5 IU), glycine (40 mg), sucrose (40 mg) and human serum albumin (25% 10 mg).	Biological	Vaccine group
Sterile Water InjectionThe vaccine diluent (sterile water for injection) is provided in a separate 1 mL ampoule.	Drug	Control group

Primary outcome

Number of self-reported new episodes of acute common infectious disease (CID), defined as any of the following: upper respiratory illness (URI) or influenza-like illness (ILI) or diarrhea (DIA) or undifferentiated febrile illness (UFI)
Time frame: Weekly self-reporting of occurrence or non-occurrence of episodes of CID for a maximum of 26 weeks, starting one week after allocation
URI is defined as (two or more of the following: runny or blocked nose/sneezing/sore throat/cough) and (absence of itchy or watery eyes). ILI is defined as [fever (feeling feverish, or an axillary, oral or otic temperature of 100°F or higher)] and (cough or sore throat). DIA is defined as three or more loose stools within a 24-hour period. UFI is defined as [fever (feeling feverish, or an axillary, oral or otic temperature of 100°F or higher)] and (not meeting the case definition of URI, ILI or DIA). To be defined as a new episode, illness must be preceded by at least one week without any CID.

7 secondary outcomes

Number of self-reported new episodes of respiratory illness (URI or ILI), DIA and UFI
Time frame: Weekly self-reporting of occurrence or non-occurrence of episodes of respiratory illness, DIA and UFI for a maximum of 26 weeks, starting one week after allocation
Number of self-reported new weekly episodes of URI
Time frame: Weekly self-reporting of occurrence or non-occurrence of episodes of URI for a maximum of 26 weeks, starting one week after allocation
Number of self-reported new weekly episodes of ILI
Time frame: Weekly self-reporting of occurrence or non-occurrence of episodes of ILI for a maximum of 26 weeks, starting one week after allocation
Number of self-reported new weekly episodes of DIA
Time frame: Weekly self-reporting of occurrence or non-occurrence of episodes of DIA for a maximum of 26 weeks, starting one week after allocation
Number of self-reported new weekly episodes of UFI
Time frame: Weekly self-reporting of occurrence or non-occurrence of episodes of UFI for a maximum of 26 weeks, starting one week after allocation
Number of clinically-confirmed episodes of CID syndromes
Time frame: 27 weeks after allocation
Number of laboratory-confirmed episodes of CID syndromes
Time frame: 27 weeks after allocation

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2021.
Derived from this study: PubMed 34127294Odita CI, Conan A, Smith-Antony M, Battice J, England S, Barry D, Gessner BD, Knobel DL. Non-specific effects of rabies vaccine on the incidence of self-reported common infectious disease episodes: A randomized controlled trial. Vaccine. 2022 Mar 8;40(11):1617-1623. doi: 10.1016/j.vaccine.2021.06.007. Epub 2021 Jun 11.
Derived from this study: PubMed 32546199Knobel D, Odita CI, Conan A, Barry D, Smith-Anthony M, Battice J, England S, Gessner BD. Non-specific effects of rabies vaccine on the incidence of common infectious disease episodes: study protocol for a randomized controlled trial. Trials. 2020 Jun 16;21(1):534. doi: 10.1186/s13063-020-04467-z.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Darryn Knobel, PhD principal investigator

Ross University School of Veterinary Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Saint Kitts and Nevis. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of self-reported new episodes of acute common infectious disease (CID), defined as any of the following: upper respiratory illness (URI) or influenza-like illness (ILI) or diarrhea (DIA) or undifferentiated febrile illness (UFI) (time frame: Weekly self-reporting of occurrence or non-occurrence of episodes of CID for a maximum of 26 weeks, starting one week after allocation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03656198, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2021.