Clincosm LogoSign in Get a demo

MALRAB: Effect of Antimalarial Drugs to Rabies Vaccine for Post-exposure Prophylaxis.

Sponsor
State University of New York - Upstate Medical University (Other)
Overall Status
Completed
CT.gov ID
NCT02564471
Collaborator
Walter Reed Army Institute of Research (WRAIR) (U.S. Fed), Kansas State University (Other)
103
Enrollment
1
Location
4
Arms
26.7
Actual Duration (Months)
3.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an exploratory trial to evaluate the effect of antimalarial drugs on the immune response generated by rabies vaccine when administered for post-exposure prophylaxis. This study will use the FDA approved post-exposure prophylaxis vaccine regimen (without rabies immune globulin) in the presence or absence of an FDA-approved malaria chemoprophylaxis regimen.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

Rabies is present on all continents where U.S. military personnel deploy, including countries where malaria is also endemic and where U.S. military personnel are required to take malaria prophylaxis. Rabies post-exposure prophylaxis in unvaccinated individuals who are not on malaria prophylaxis consists of four, 1.0-mL intramuscular (IM) injections of the purified chick embryo cell (PCECV) rabies vaccine on days 0, 3, 7, and 14. The current Advisory Committee on Immunization Practices (ACIP) guidelines recommend that exposed persons who are taking malaria prophylaxis should receive a fifth dose of rabies vaccine 28 days after the exposure. These guidelines do not differentiate between drugs used for malaria prophylaxis This study will administer the post-exposure regimen to volunteers from a US population of military age who are taking one of three malaria prophylaxis regimens or no malaria prophylaxis. The goal of this study is to asses if individuals on malaria prophylaxis achieve the required rabies titer after completion of the four dose regimen.

Obtaining rabies vaccine and rabies immune globulin in a deployed setting can be challenging. A full understanding of the requirements for protecting exposed individuals is necessary for appropriate decision making in a resource-constrained environment.

Study Design

Study Type:
Interventional
Actual Enrollment :
103 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Effect of Antimalarial Drugs on the Immune Response to Rabies Vaccine for Post-exposure Prophylaxis. A Randomized, Open Label, Trial in Healthy US Adults Age 18-60 Years
Actual Study Start Date :
Nov 11, 2016
Actual Primary Completion Date :
Aug 1, 2018
Actual Study Completion Date :
Feb 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Chloroquine

Chloroquine Phosphate tablet for oral administration 500 mg chloroquine phosphate (equivalent to 300 mg base)

Drug: Chloroquine
FDA approve dosing schedule
Other Names:
  • Chloroquine Phosphate

    • Biological: Rabies Vaccine
    FDA approve dosing schedule
    Other Names:
  • RabAvert

    		•
    Experimental: Atovaquone and Proguanil (Malarone)

    Malarone tablet for oral administration 250 mg atovaquone and 100 mg proguanil hydrochloride. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen.

    Drug: Atovaquone and Proguanil
    FDA approve dosing schedule
    Other Names:
  • Malarone

    • Biological: Rabies Vaccine
    FDA approve dosing schedule
    Other Names:
  • RabAvert

    		•
    Experimental: Doxycycline

    Doxycycline hyclate tablet for oral administration, contains specially coated pellets of doxycycline hyclate equivalent to 100 mg of doxycycline. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen.

    Drug: Doxycycline
    FDA approve dosing schedule
    Other Names:
  • Doxycycline Hyclate

    • Biological: Rabies Vaccine
    FDA approve dosing schedule
    Other Names:
  • RabAvert

    		•
    Active Comparator: Rabies

    RabAvert rabies vaccine, at least 2.5 IU of rabies antigen.

    Biological: Rabies Vaccine
    FDA approve dosing schedule
    Other Names:
  • RabAvert

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Geometric Mean Titer (GMT) 14 Days Post Fourth Dose Post Exposure Prophylaxis (PEP) With Purified Chick Embryo Cell Vaccine (PCECV) in Each Malaria Prophylaxis Group Compared to Control to Determine if a Fifth Dose of PEP Would Add Value [6 weeks for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups and at 4 weeks for Rabies Group]

      Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups received antimalarial up to day 14 and rabies vaccinations on day 14, 17, 21, and 28 (dose 4). Rabies Group received the rabies vaccination on days 0, 3,7 and 14 (dose 4). Rabies virus-specific serum antibody neutralization assay was used to measure rabies virus antibodies, using the rapid fluorescent foci inhibition test (RFFIT). A titer of >0.5 IU/ml against rabies virus as protective. Descriptive analyses were based on samples taken 14 days after dose 4, (e.g., at 6 weeks for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Arms and at 4 weeks for Rabies Arm).

    Secondary Outcome Measures

    1. GMT Over Protective Titer Prior to Third Dose of PCECV [21 days for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups and 7 days for Rabies Arm]

      Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups received antimalarial up to day 14 and rabies vaccinations on day 14, 17, 21 (dose 3), and 28 (dose 4). Rabies Group received the rabies vaccination on days 0, 3, 7 (dose 3) and 14 (dose 4). For Chloroquine, Malarone and Doxycycline Groups, samples were taken on days 0, 21, 28 and 56. For Rabies Group, samples were taken on days 0, 7, 14 and 42. Rabies virus-specific serum antibody neutralization assay was used to measure rabies virus antibodies, using the rapid fluorescent foci inhibition test (RFFIT). A titer of >0.5 IU/ml against rabies virus as protective.

    2. GMT Over Protective Titer Prior Fourth Dose of PCECV [28 days for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups and 14 days for Rabies Arm]

      Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups received antimalarial up to day 14 and rabies vaccinations on day 14, 17, 21 (dose 3), and 28 (dose 4). Rabies Group received the rabies vaccination on days 0, 3, 7 (dose 3) and 14 (dose 4). For Chloroquine, Malarone and Doxycycline Groups, samples were taken on days 0, 21, 28 and 56. For Rabies Group, samples were taken on days 0, 7, 14 and 42. Rabies virus-specific serum antibody neutralization assay was used to measure rabies virus antibodies, using the rapid fluorescent foci inhibition test (RFFIT). A titer of >0.5 IU/ml against rabies virus as protective.

    3. GMT Over Protective Titer 28 Days Post Fourth Dose of PCECV [Up to 8 weeks for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups and up to 6 weeks for Rabies Arm]

      Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups received antimalarial up to day 14 and rabies vaccinations on day 14, 17, 21 (dose 3), and 28 (dose 4). Rabies Group received the rabies vaccination on days 0, 3,7 (dose 3) and 14 (dose 4). For Chloroquine, Malarone and Doxycycline Groups, samples were taken on days 0, 21, 28 and 56. For Rabies Group, samples were taken on days 0, 7, 14 and 42. Rabies virus-specific serum antibody neutralization assay was used to measure rabies virus antibodies, using the rapid fluorescent foci inhibition test (RFFIT). A titer of >0.5 IU/ml against rabies virus as protective.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    1. Provide signed and dated informed consent form.

    2. Willing to comply with all study procedures and be available for the duration of the study.

    3. Male or female, aged ≥ 18 to ≤ 60 years on day of inclusion.

    4. In good general health based on medical history and physical exam

    Exclusion Criteria:

    1. Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination.

    2. Participation in the 4 weeks preceding the first trial vaccination, or planned participation during the present trial period, in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.

    3. Previous history of receiving the rabies vaccine.

    4. Previous history of receiving rabies immune globulin.

    5. Any major psychiatric disorder, such as severe depression, severe anxiety disorder, psychosis, schizophrenia, other major psychiatric disorders, or seizures. History of mild depression or anxiety disorder that are well controlled are not exclusion criteria.

    6. Use of any immunosuppressive drug at the time of the study or 30 days previously. Topical steroids will not be considered an immunosuppressive drug and their use will not be considered an exclusion criteria.

    7. Any immunosuppressive disorder, such as HIV infection, common variable immunodeficiency, active cancers or chemotherapy.

    8. History of renal insufficiency or requiring dialysis.

    9. Have any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

    10. Identified as an employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the employee or the Investigator.

    11. Previous adverse reaction to any of the antimalarial drugs used in this study.

    Temporary Exclusion Criteria: Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]) on day 0.. A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided. If the delay for the febrile illness exceeds the window between screening and vaccination, or if deemed necessary by the investigator, a prospective subject may be re-screened once the fever has resolved.

    Recent or scheduled receipt of any vaccine 4 weeks prior to day 0.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 State University of New York, Upstate Medical University (SUNY-UMU) Syracuse New York United States 13210

    Sponsors and Collaborators

    • State University of New York - Upstate Medical University
    • Walter Reed Army Institute of Research (WRAIR)
    • Kansas State University

    Investigators

    • Principal Investigator: Timothy Endy, MD, State University of New York - Upstate Medical University

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Timothy Endy, MD MPH, Chair, Department of Microbiology and Immunology, State University of New York - Upstate Medical University
    ClinicalTrials.gov Identifier:
    NCT02564471
    Other Study ID Numbers:
    • 790117
    First Posted:
    Sep 30, 2015
    Last Update Posted:
    May 13, 2021
    Last Verified:
    Apr 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:
    Rabies
    Doxycycline
    Chloroquine
    Chloroquine diphosphate
    Atovaquone
    Proguanil

    Study Results

    Participant Flow

    Recruitment Details Healthy adults aged 18 to 60 were recruited from 11-Nov-2016 to 07-Jun-2018 in and around the study site in Syracuse, New York
    Pre-assignment Detail
    Arm/Group Title Chloroquine Atovaquone and Proguanil (Malarone) Doxycycline Rabies
    Arm/Group Description Chloroquine Phosphate tablet for oral administration 500 mg chloroquine phosphate (equivalent to 300 mg base) Chloroquine: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Malarone tablet for oral administration 250 mg atovaquone and 100 mg proguanil hydrochloride. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Atovaquone and Proguanil: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Doxycycline hyclate tablet for oral administration, contains specially coated pellets of doxycycline hyclate equivalent to 100 mg of doxycycline. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Doxycycline: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Rabies Vaccine: FDA approve dosing schedule
    Period Title: Overall Study
    STARTED 25 26 27 25
    COMPLETED 22 23 24 25
    NOT COMPLETED 3 3 3 0

    Baseline Characteristics

    Arm/Group Title Chloroquine Atovaquone and Proguanil (Malarone) Doxycycline Rabies Total
    Arm/Group Description Chloroquine Phosphate tablet for oral administration 500 mg chloroquine phosphate (equivalent to 300 mg base) Chloroquine: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Malarone tablet for oral administration 250 mg atovaquone and 100 mg proguanil hydrochloride. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Atovaquone and Proguanil: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Doxycycline hyclate tablet for oral administration, contains specially coated pellets of doxycycline hyclate equivalent to 100 mg of doxycycline. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Doxycycline: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Rabies Vaccine: FDA approve dosing schedule Total of all reporting groups
    Overall Participants 20 23 23 25 91
    Age (Count of Participants)
    <=18 years
    1
    5%
    0
    0%
    1
    4.3%
    0
    0%
    2
    2.2%
    Between 18 and 65 years
    19
    95%
    23
    100%
    22
    95.7%
    25
    100%
    89
    97.8%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    12
    60%
    16
    69.6%
    13
    56.5%
    11
    44%
    52
    57.1%
    Male
    8
    40%
    7
    30.4%
    10
    43.5%
    14
    56%
    39
    42.9%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    5%
    3
    13%
    2
    8.7%
    0
    0%
    6
    6.6%
    Not Hispanic or Latino
    19
    95%
    20
    87%
    21
    91.3%
    25
    100%
    85
    93.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    1
    4.3%
    0
    0%
    2
    8%
    3
    3.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    10%
    2
    8.7%
    1
    4.3%
    5
    20%
    10
    11%
    White
    18
    90%
    20
    87%
    22
    95.7%
    18
    72%
    78
    85.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    20
    100%
    23
    100%
    23
    100%
    25
    100%
    91
    100%
    Participants with data available at both baseline and post baseline assessments (participants) [Number]
    Number [participants]
    20
    100%
    23
    100%
    23
    100%
    25
    100%
    91
    100%

    Outcome Measures

    1. Primary Outcome
    Title Geometric Mean Titer (GMT) 14 Days Post Fourth Dose Post Exposure Prophylaxis (PEP) With Purified Chick Embryo Cell Vaccine (PCECV) in Each Malaria Prophylaxis Group Compared to Control to Determine if a Fifth Dose of PEP Would Add Value
    Description Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups received antimalarial up to day 14 and rabies vaccinations on day 14, 17, 21, and 28 (dose 4). Rabies Group received the rabies vaccination on days 0, 3,7 and 14 (dose 4). Rabies virus-specific serum antibody neutralization assay was used to measure rabies virus antibodies, using the rapid fluorescent foci inhibition test (RFFIT). A titer of >0.5 IU/ml against rabies virus as protective. Descriptive analyses were based on samples taken 14 days after dose 4, (e.g., at 6 weeks for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Arms and at 4 weeks for Rabies Arm).
    Time Frame 6 weeks for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups and at 4 weeks for Rabies Group

    Outcome Measure Data

    Analysis Population Description
    Group 1: 1 subject was excluded from analysis due to presence of rabies antibody titer at baseline, 1 was excluded due to use of steroids during the study; Group 2: 1 subject completed primary endpoint but did not complete the study; Group 3: 1 subject was excluded from analysis due to presence of rabies antibody titer at baseline
    Arm/Group Title Chloroquine Atovaquone and Proguanil (Malarone) Doxycycline Rabies
    Arm/Group Description Chloroquine Phosphate tablet for oral administration 500 mg chloroquine phosphate (equivalent to 300 mg base) Chloroquine: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Malarone tablet for oral administration 250 mg atovaquone and 100 mg proguanil hydrochloride. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Atovaquone and Proguanil: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Doxycycline hyclate tablet for oral administration, contains specially coated pellets of doxycycline hyclate equivalent to 100 mg of doxycycline. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Doxycycline: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Rabies Vaccine: FDA approve dosing schedule
    Measure Participants 20 24 23 25
    Geometric Mean (Geometric Coefficient of Variation) [IU/ml]
    3.45
    (1.62)
    7.95
    (0.81)
    8.51
    (0.94)
    10.26
    (0.66)
    2. Secondary Outcome
    Title GMT Over Protective Titer Prior to Third Dose of PCECV
    Description Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups received antimalarial up to day 14 and rabies vaccinations on day 14, 17, 21 (dose 3), and 28 (dose 4). Rabies Group received the rabies vaccination on days 0, 3, 7 (dose 3) and 14 (dose 4). For Chloroquine, Malarone and Doxycycline Groups, samples were taken on days 0, 21, 28 and 56. For Rabies Group, samples were taken on days 0, 7, 14 and 42. Rabies virus-specific serum antibody neutralization assay was used to measure rabies virus antibodies, using the rapid fluorescent foci inhibition test (RFFIT). A titer of >0.5 IU/ml against rabies virus as protective.
    Time Frame 21 days for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups and 7 days for Rabies Arm

    Outcome Measure Data

    Analysis Population Description
    Group 1: 1 subject completed all doses of vaccine but did not complete the study; Group 2: 2 subjects completed all doses of vaccine but did not complete the study.
    Arm/Group Title Chloroquine Atovaquone and Proguanil (Malarone) Doxycycline Rabies
    Arm/Group Description Chloroquine Phosphate tablet for oral administration 500 mg chloroquine phosphate (equivalent to 300 mg base) Chloroquine: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Malarone tablet for oral administration 250 mg atovaquone and 100 mg proguanil hydrochloride. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Atovaquone and Proguanil: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Doxycycline hyclate tablet for oral administration, contains specially coated pellets of doxycycline hyclate equivalent to 100 mg of doxycycline. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Doxycycline: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Rabies Vaccine: FDA approve dosing schedule
    Measure Participants 21 25 23 25
    Geometric Mean (Geometric Coefficient of Variation) [IU/ml]
    0.14
    (0.62)
    0.11
    (0.40)
    0.16
    (0.72)
    0.17
    (1.15)
    3. Secondary Outcome
    Title GMT Over Protective Titer Prior Fourth Dose of PCECV
    Description Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups received antimalarial up to day 14 and rabies vaccinations on day 14, 17, 21 (dose 3), and 28 (dose 4). Rabies Group received the rabies vaccination on days 0, 3, 7 (dose 3) and 14 (dose 4). For Chloroquine, Malarone and Doxycycline Groups, samples were taken on days 0, 21, 28 and 56. For Rabies Group, samples were taken on days 0, 7, 14 and 42. Rabies virus-specific serum antibody neutralization assay was used to measure rabies virus antibodies, using the rapid fluorescent foci inhibition test (RFFIT). A titer of >0.5 IU/ml against rabies virus as protective.
    Time Frame 28 days for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups and 14 days for Rabies Arm

    Outcome Measure Data

    Analysis Population Description
    Group 1: 1 subject received all doses but did not complete the study; Group 2: 2 subjects received all doses but did not complete the study.
    Arm/Group Title Chloroquine Atovaquone and Proguanil (Malarone) Doxycycline Rabies
    Arm/Group Description Chloroquine Phosphate tablet for oral administration 500 mg chloroquine phosphate (equivalent to 300 mg base) Chloroquine: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Malarone tablet for oral administration 250 mg atovaquone and 100 mg proguanil hydrochloride. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Atovaquone and Proguanil: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Doxycycline hyclate tablet for oral administration, contains specially coated pellets of doxycycline hyclate equivalent to 100 mg of doxycycline. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Doxycycline: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Rabies Vaccine: FDA approve dosing schedule
    Measure Participants 21 25 23 25
    Geometric Mean (Geometric Coefficient of Variation) [IU/ml]
    4.15
    (289)
    6.45
    (1.39)
    7.04
    (2.71)
    6.98
    (1.12)
    4. Secondary Outcome
    Title GMT Over Protective Titer 28 Days Post Fourth Dose of PCECV
    Description Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups received antimalarial up to day 14 and rabies vaccinations on day 14, 17, 21 (dose 3), and 28 (dose 4). Rabies Group received the rabies vaccination on days 0, 3,7 (dose 3) and 14 (dose 4). For Chloroquine, Malarone and Doxycycline Groups, samples were taken on days 0, 21, 28 and 56. For Rabies Group, samples were taken on days 0, 7, 14 and 42. Rabies virus-specific serum antibody neutralization assay was used to measure rabies virus antibodies, using the rapid fluorescent foci inhibition test (RFFIT). A titer of >0.5 IU/ml against rabies virus as protective.
    Time Frame Up to 8 weeks for Chloroquine, Atovaquone and Proguanil (Malarone) and Doxycycline Groups and up to 6 weeks for Rabies Arm

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Chloroquine Atovaquone and Proguanil (Malarone) Doxycycline Rabies
    Arm/Group Description Chloroquine Phosphate tablet for oral administration 500 mg chloroquine phosphate (equivalent to 300 mg base) Chloroquine: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Malarone tablet for oral administration 250 mg atovaquone and 100 mg proguanil hydrochloride. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Atovaquone and Proguanil: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Doxycycline hyclate tablet for oral administration, contains specially coated pellets of doxycycline hyclate equivalent to 100 mg of doxycycline. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Doxycycline: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Rabies Vaccine: FDA approve dosing schedule
    Measure Participants 20 23 23 25
    Geometric Mean (Geometric Coefficient of Variation) [IU/ml]
    2.3
    (1.53)
    4.96
    (0.78)
    5.18
    (1.14)
    6.87
    (1.04)

    Adverse Events

    Time Frame 8 weeks from Chloroquine, Malarone/Atovaquone, Doxycyline groups, 6 weeks for rabies control group.
    Adverse Event Reporting Description
    Arm/Group Title Chloroquine Atovaquone and Proguanil (Malarone) Doxyclycline Rabies
    Arm/Group Description Chloroquine Phosphate tablet for oral administration 500 mg chloroquine phosphate (equivalent to 300 mg base) Chloroquine: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Malarone tablet for oral administration 250 mg atovaquone and 100 mg proguanil hydrochloride. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Atovaquone and Proguanil: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule Doxycycline hyclate tablet for oral administration, contains specially coated pellets of doxycycline hyclate equivalent to 100 mg of doxycycline. RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Doxycycline: FDA approve dosing schedule Rabies Vaccine: FDA approve dosing schedule RabAvert rabies vaccine, at least 2.5 IU of rabies antigen. Rabies Vaccine: FDA approve dosing schedule
    All Cause Mortality
    Chloroquine Atovaquone and Proguanil (Malarone) Doxyclycline Rabies
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/25 (0%) 0/26 (0%) 0/27 (0%) 0/25 (0%)
    Serious Adverse Events
    Chloroquine Atovaquone and Proguanil (Malarone) Doxyclycline Rabies
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/25 (0%) 0/26 (0%) 0/27 (0%) 0/25 (0%)
    Other (Not Including Serious) Adverse Events
    Chloroquine Atovaquone and Proguanil (Malarone) Doxyclycline Rabies
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 17/25 (68%) 22/26 (84.6%) 19/27 (70.4%) 19/25 (76%)
    Gastrointestinal disorders
    Abdominal Pain 4/25 (16%) 3/23 (13%) 0/23 (0%) 0 0/25 (0%) 0
    Nausea 4/20 (20%) 4/26 (15.4%) 6/23 (26.1%) 4/25 (16%)
    Diarrhea 5/25 (20%) 5/26 (19.2%) 2/27 (7.4%) 0/25 (0%)
    Vomiting 1/25 (4%) 3/26 (11.5%) 1/27 (3.7%) 1/25 (4%)
    General disorders
    Injection site reaction 9/25 (36%) 11/26 (42.3%) 10/27 (37%) 13/25 (52%)
    Flu like symptoms 3/25 (12%) 1/26 (3.8%) 2/27 (7.4%) 2/25 (8%)
    Fatigue 1/25 (4%) 1/26 (3.8%) 4/27 (14.8%) 0/25 (0%)
    Infections and infestations
    Upper Respiratory Infection 1/25 (4%) 4/26 (15.4%) 2/27 (7.4%) 4/25 (16%)
    Injury, poisoning and procedural complications
    Burn 0/25 (0%) 0/26 (0%) 2/27 (7.4%) 0/25 (0%)
    Musculoskeletal and connective tissue disorders
    Myalgia 3/25 (12%) 4/26 (15.4%) 3/27 (11.1%) 1/25 (4%)
    Nervous system disorders
    Headache 4/25 (16%) 9/26 (34.6%) 7/27 (25.9%) 3/25 (12%)
    Dizziness 2/25 (8%) 1/26 (3.8%) 1/27 (3.7%) 0/25 (0%)
    Respiratory, thoracic and mediastinal disorders
    Laryngeal Inflammation 1/25 (4%) 2/26 (7.7%) 1/27 (3.7%) 0/25 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT 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.

    Results Point of Contact

    Name/Title Dr. Timothy Endy
    Organization SUNY Upstate Medical University
    Phone 3154647692
    Email endyt@upstate.edu
    Responsible Party:
    Timothy Endy, MD MPH, Chair, Department of Microbiology and Immunology, State University of New York - Upstate Medical University
    ClinicalTrials.gov Identifier:
    NCT02564471
    Other Study ID Numbers:
    • 790117
    First Posted:
    Sep 30, 2015
    Last Update Posted:
    May 13, 2021
    Last Verified:
    Apr 1, 2021