<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03297671</url>
  </required_header>
  <id_info>
    <org_study_id>Rh Study</org_study_id>
    <nct_id>NCT03297671</nct_id>
  </id_info>
  <brief_title>The Prevention of Rh Disease of Newborns in Pakistan</brief_title>
  <official_title>Early Identification of Rh Negative Women During Pregnancy and Use of Prophylaxis to Prevent Rh Disease of Newborns in Dadu District, Sindh, Pakistan</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aga Khan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Hospital for Sick Children</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Grand Challenges Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Aga Khan University</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators aim to demonstrate the feasibility of point-of-care identification of&#xD;
      Rh-negative women in a poor, rural setting in Pakistan. Feasibility will be assessed across 2&#xD;
      major domains: 1) acceptance by pregnant women to receive the point-of-care test; and, 2)&#xD;
      ability of health workers to administer the point of care test and interpret results. The&#xD;
      investigators will also measure whether RhIg prophylaxis can be successfully delivered and is&#xD;
      accepted by pregnant women in this setting. The socio-demographic correlates of the&#xD;
      acceptance of point-of-care testing and where applicable, the acceptance of RhIg prophylaxis&#xD;
      will also be assessed. In addition, the investigators will also explore the baseline&#xD;
      knowledge of Rh disease among pregnant women and lady health visitors in this study&#xD;
      population and will investigate socio-demographic correlates of baseline knowledge and the&#xD;
      uptake of knowledge among pregnant women. Finally, the prevalence of Rh negativity will be&#xD;
      calculated and stillbirth and neonatal mortality will be tracked among all participants. All&#xD;
      stillbirths and neonatal deaths in this population will be characterized with respect to&#xD;
      cause and Rh-negativity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Rhesus (Rh) disease is a preventable condition caused by an incompatibility between maternal&#xD;
      and fetal red blood cells (RBCs). If a person's RBCs lacks a certain protein s/he is said to&#xD;
      be Rh-negative. Similarly, if a person's RBCs have that same protein, s/he is said to be&#xD;
      Rh-positive. If a pregnant woman's is Rh-negative and her fetus is Rh-positive, the baby is&#xD;
      at risk of Rh disease. The complications associated with Rh disease include miscarriage,&#xD;
      stillbirth, and neonatal death. Among surviving newborns, Rh disease can cause anemia (low&#xD;
      RBCs, which can appear as feeling tired or weak or having a shortness of breath), jaundice&#xD;
      (yellowing of the skin), and brain damage. If Rh-negative women are identified, there is a&#xD;
      very high chance that Rh disease of the newborn can be prevented.&#xD;
&#xD;
      The purpose of this study is to demonstrate the feasibility of point-of-care identification&#xD;
      of Rh-negative women in Dadu district, Pakistan. Determining the Rh status of pregnant women&#xD;
      is the first step towards prevention of Rh disease of the newborn. By collecting information&#xD;
      about a) the Rh status and blood type of pregnant women; b) the acceptability of a point of&#xD;
      care test blood test of Rh disease; and, c) the acceptability of treatment for Rh negativity&#xD;
      in pregnant women, the investigators will be able to improve antenatal care and prevent Rh&#xD;
      disease of the newborn in rural settings. The implementation of a point-of-care Rh test will&#xD;
      allow us for the identification of Rh-negative women, prompt provision of treatment, and&#xD;
      prevention of Rh disease of the newborn in rural settings in Pakistan.&#xD;
&#xD;
      As part of this study, participants will be asked a series of questions to assess&#xD;
      reproductive history of pregnant women and other demographic characteristics (i.e. questions&#xD;
      about home environment and lifestyle). The investigators will also ask whether they are&#xD;
      willing to provide a drop of blood, collected via finger prick, to allow us to determine your&#xD;
      Rh status by ELDONCARD. If Rh test reveals that the pregnant women are Rh negative, the&#xD;
      investigators will offer them up to two doses of treatment, first at approximately 28 weeks&#xD;
      of gestation and again within 72 hours of delivery. The injections will be administered at&#xD;
      the health facility. They will also be asked to undergo an ultrasound procedure by a trained&#xD;
      technician at health facility. Moreover, after the newborn is delivered, the investigators&#xD;
      will also ask a series of question and perform an in-person assessment of newborn to assess&#xD;
      their health within 72 hours of delivery and then again on their 29th day of life. If they&#xD;
      are found to be Rh-negative and they have a miscarriage, stillbirth, or baby dies within the&#xD;
      first month of life, the investigators will ask them if we can collect a sample of their&#xD;
      blood for further testing.&#xD;
&#xD;
      The investigators will conduct a prospective cohort study in Tehsil Headquarter Hospital&#xD;
      (THQ) and District Headquarter Hospital (DHQ) that are situated in Dadu District, Sindh,&#xD;
      Pakistan. In total, between 3 and 5 Lady Health Visitors (LHVs) will be enrolled at the study&#xD;
      THQ and DHQ to administer the point-of-care test and if necessary, prophylaxis. Over the&#xD;
      course of the study period, approximately 2000 pregnant women will be enrolled in total&#xD;
      (across both study sites); liveborn newborns delivered to enrolled pregnant women will be&#xD;
      followed for the first month of life. The sample size of 2000 pregnant women in this study is&#xD;
      driven by the estimated prevalence of Rh negativity in the population (7%) and hence, the&#xD;
      number of women investigators expect to offer two injections of RhIg (n=140). A sample size&#xD;
      of 140 participants will enable us to measure the acceptance RhIg by pregnant women.&#xD;
&#xD;
      This prospective cohort will include two groups of participants: a) between 3 and 5 LHVs who&#xD;
      are full time employees at THQ Johi and DHQ Dadu and, b) 2000 pregnant women from the&#xD;
      communities in the catchment area of THQ Johi and DHQ Dadu.&#xD;
&#xD;
      To address one of our study aims, a single questionnaire will be administered to a cadre of&#xD;
      approximately 30 health professionals (i.e., physicians, lady health visitors, nurses, etc.)&#xD;
      who are not otherwise engaged in study activities.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 27, 2018</start_date>
  <completion_date type="Actual">February 28, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of pregnant women who will accept the point of care ELDONCARD test</measure>
    <time_frame>12 months</time_frame>
    <description>Acceptability of the point-of-care test will be represented as the proportion of positive (i.e., Yes) responses to each of the 6 questions listed below. The acceptability of the test between sites will be compared.&#xD;
Did the participant agree to have the point-of-care test?&#xD;
Do you think that having the point-of-care test will provide information that could improve the health of your newborn?&#xD;
Do you think the point-of-care test was safe?&#xD;
Did your family approve of you having the point-of-care test?&#xD;
Would you recommend the point of care test to other mothers in the village?&#xD;
In the future, would you agree to have this point of care test again?</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prevalence of Rhesus negativity in pregnant women</measure>
    <time_frame>12 months</time_frame>
    <description>Prevalence of Rhesus negativity will be calculated from the total sample size of pregnant women (2000) for the study and the total number of Rhesus-negative women (0-2000) actually identified during the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of lady health visitors who will correctly perform point-of-care test and interpret the results of the point-of-care test</measure>
    <time_frame>12 months</time_frame>
    <description>Ability of each lady health visitor to perform point-of-care test, each time a test is performed, a composite score (0-16) will be generated that takes into account all 16 steps of the standardized operational protocol. Composite test scores (0-16) will be plotted over time, where time will be evaluated in increments of days, weeks, and months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of positive responses on knowledge pertaining to Rhesus disease in pregnant women and lady health visitors</measure>
    <time_frame>12 months</time_frame>
    <description>Knowledge uptake will be assessed in both pregnant women and lady health visitors by comparing their baseline assessments with those completed at the close of the study (proportion of positive (i.e., Yes) responses).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of pregnant women who will accept RhIg prophylaxis</measure>
    <time_frame>12 months</time_frame>
    <description>Acceptability of RhIg prophylaxis will be represented as the proportion of positive (i.e., Yes) responses to each of the 6 questions listed below. The acceptability of RhIg prophylaxis between sites will be compared.&#xD;
Did the participant verbally agree to receive prophylaxis?&#xD;
Do you think that receiving prophylaxis may improve the health of your newborn?&#xD;
Do you think that receiving prophylaxis was safe?&#xD;
Did your family approve of you receiving prophylaxis?&#xD;
Would you recommend receiving prophylaxis to other Rhesus-negative mothers in the village?&#xD;
In future pregnancies, would you agree to receive more injections of RhIg prophylaxis? We will also report the proportion of participants who agreed to receive 1 and/or 2 doses of RhIg in total, and by site.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of stillbirths and neonatal deaths per 1000 live births in this population with respect to cause and Rhesus-negativity</measure>
    <time_frame>13 months</time_frame>
    <description>Rate of stillbirths and newborn deaths will be tracked throughout the study and rates will be presented per 1000 live births. Finally, we will also report mean and median antibody titers for all Rhesus-negative women who have a miscarriage, stillbirth, or their newborns die within the first month of life.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">1654</enrollment>
  <condition>Rhesus Disease</condition>
  <condition>Anti-D (Rh) Antibodies Affecting Care of Mother</condition>
  <arm_group>
    <arm_group_label>Pregnant Women</arm_group_label>
    <description>2000 pregnant women from the communities in the catchment area of THQ Johi and DHQ Dadu. Rh negative women will receive two RhIg prophylaxis injections.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lady Health Visitors (LHVs)</arm_group_label>
    <description>3-5 LHVs who are full time employees at THQ Johi and DHQ Dadu. LHVs will perform ELDONCARD test and provide RhIg prophylaxis injections.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RhIg prophylaxis</intervention_name>
    <description>Two RhIg prophylaxis injections for Rh negative women</description>
    <arm_group_label>Lady Health Visitors (LHVs)</arm_group_label>
    <arm_group_label>Pregnant Women</arm_group_label>
    <other_name>Training on Rh disease</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>ELDONCARD</intervention_name>
    <description>ELDONCARD point-of-care test.</description>
    <arm_group_label>Lady Health Visitors (LHVs)</arm_group_label>
    <arm_group_label>Pregnant Women</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>ELDONCARD Test</intervention_name>
    <description>LHVs will perform ELDONCARD test.</description>
    <arm_group_label>Lady Health Visitors (LHVs)</arm_group_label>
    <arm_group_label>Pregnant Women</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Study population will be LHVs, pregnant women and non-study health care professional&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion criteria for pregnant women&#xD;
&#xD;
          -  Pregnant women who present to THQ Johi and DHQ Dadu for ANC&#xD;
&#xD;
          -  At least 13 weeks gestation (assessed using self-reported first day of last menstrual&#xD;
             period)&#xD;
&#xD;
          -  Currently resides within one of 5 Union Council's surrounding THQ Johi and in the&#xD;
             catchment area of DHQ Dadu at a fixed address&#xD;
&#xD;
          -  Intends to deliver and remain in study catchment area for 1-month after the delivery&#xD;
             of their newborn(s)&#xD;
&#xD;
          -  Provides written informed consent&#xD;
&#xD;
          -  Was not previously enrolled in this study during a different pregnancy&#xD;
&#xD;
        Exclusion criteria for pregnant women&#xD;
&#xD;
          -  Previously consented into this study&#xD;
&#xD;
          -  Reported that they previously had an anaphylactic reaction to an injection of an&#xD;
             antibody blood product&#xD;
&#xD;
          -  Has any chronic disease related to the heart, liver, kidney, or lungs&#xD;
&#xD;
          -  Does not currently reside within the study's catchment area&#xD;
&#xD;
          -  Intends to deliver outside of the catchment area&#xD;
&#xD;
          -  Plans to relocate outside of the catchment area within 1-month after the delivery of&#xD;
             their newborn(s)&#xD;
&#xD;
          -  Does not provide written consent&#xD;
&#xD;
        Inclusion criteria for lady health visitors&#xD;
&#xD;
          -  Working full-time at THQ Johi and DHQ Dadu as a Lady Health Visitor&#xD;
&#xD;
          -  Verbal consent provided from LHV's direct supervisor&#xD;
&#xD;
          -  LHV provides verbal consent to complete a test on baseline knowledge of Rh disease and&#xD;
             jaundice&#xD;
&#xD;
          -  LHV can attend a 1 day training and orientation session&#xD;
&#xD;
          -  LHV provides written informed consent to participate in study&#xD;
&#xD;
        Exclusion criteria for health care workers&#xD;
&#xD;
          -  Verbal consent not provided from LHV's direct supervisor&#xD;
&#xD;
          -  Does not consent to completing a test on baseline knowledge of Rh disease and jaundice&#xD;
&#xD;
          -  Cannot attend a 1 day training and orientation session&#xD;
&#xD;
          -  Does not provide written informed consent to participate in study&#xD;
&#xD;
        Non-study health care professional recruitment&#xD;
&#xD;
        A convenience sample of approximately 30 health care professionals including physicians,&#xD;
        LHVs, nurses, lady health workers, and midwives, who are not otherwise engaged in study&#xD;
        activities will be identified and approached at THQ Johi, DHQ Dadu, and other surrounding&#xD;
        health care facilities. To be eligible for participation, health care professionals must&#xD;
        not be employed by the study or enrolled in the study as a participant. If health care&#xD;
        professionals are determined eligible, they will be asked to complete a short questionnaire&#xD;
        to assess their knowledge of Rh disease, similar to the questionnaire administered to LHVs.&#xD;
        These health care professionals will not be enrolled into the study or followed&#xD;
        prospectively and thus, only verbal consent will be obtained.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>49 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Sajid B Soofi, FCPS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aga Khan University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gul N Khan, MPH</last_name>
    <role>Study Director</role>
    <affiliation>Aga Khan University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Shaun Morris, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital for Sick-kids Canada</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Shabina Ariff, FCPS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aga Khan University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sidrah Nausheen, FCPS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aga Khan University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lisa Pell, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital for Sick-kids Canada</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Alvin Zipursky, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Eldon Biologicals A/S</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Taluka Headquarter Hospital Johi and District Headquarter Hospital Dadu</name>
      <address>
        <city>Dādu</city>
        <state>Sindh</state>
        <zip>74800</zip>
        <country>Pakistan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <results_reference>
    <citation>Zipursky A, Bhutani VK. Impact of Rhesus disease on the global problem of bilirubin-induced neurologic dysfunction. Semin Fetal Neonatal Med. 2015 Feb;20(1):2-5. doi: 10.1016/j.siny.2014.12.001. Epub 2015 Jan 9.</citation>
    <PMID>25582277</PMID>
  </results_reference>
  <results_reference>
    <citation>Fung Kee Fung K, Eason E, Crane J, Armson A, De La Ronde S, Farine D, Keenan-Lindsay L, Leduc L, Reid GJ, Aerde JV, Wilson RD, Davies G, Desilets VA, Summers A, Wyatt P, Young DC; Maternal-Fetal Medicine Committee, Genetics Committee. Prevention of Rh alloimmunization. J Obstet Gynaecol Can. 2003 Sep;25(9):765-73. doi: 10.1016/s1701-2163(16)31006-4.</citation>
    <PMID>12970812</PMID>
  </results_reference>
  <results_reference>
    <citation>ELDON K. Simultaneous ABO and Rh groupings on cards in the laboratory or at the bedside. Dan Med Bull. 1955 Mar;2(2):33-40. No abstract available.</citation>
    <PMID>14379729</PMID>
  </results_reference>
  <results_reference>
    <citation>Biologicals, E. Clinical Evidence - Comparative Study of EldonCards. 2012</citation>
  </results_reference>
  <results_reference>
    <citation>Zipursky A, Paul VK. The global burden of Rh disease. Arch Dis Child Fetal Neonatal Ed. 2011 Mar;96(2):F84-5. doi: 10.1136/adc.2009.181172. Epub 2010 Oct 30. No abstract available.</citation>
    <PMID>21037283</PMID>
  </results_reference>
  <results_reference>
    <citation>World Health Organization, U., Handbook IMCI. Integrated Management of Childhood Illness. 2005.</citation>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>September 26, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>July 8, 2020</last_update_submitted>
  <last_update_submitted_qc>July 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Aga Khan University</investigator_affiliation>
    <investigator_full_name>Dr Sajid Bashir Soofi</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is not a plan to make individual participant data available.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03297671
org study id: Rh Study
nct id: NCT03297671
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: Yes
is us export: No
The investigators aim to demonstrate the feasibility of point-of-care identification of
      Rh-negative women in a poor, rural setting in Pakistan. Feasibility will be assessed across 2
      major domains: 1) acceptance by pregnant women to receive the point-of-care test; and, 2)
      ability of health workers to administer the point of care test and interpret results. The
      investigators will also measure whether RhIg prophylaxis can be successfully delivered and is
      accepted by pregnant women in this setting. The socio-demographic correlates of the
      acceptance of point-of-care testing and where applicable, the acceptance of RhIg prophylaxis
      will also be assessed. In addition, the investigators will also explore the baseline
      knowledge of Rh disease among pregnant women and lady health visitors in this study
      population and will investigate socio-demographic correlates of baseline knowledge and the
      uptake of knowledge among pregnant women. Finally, the prevalence of Rh negativity will be
      calculated and stillbirth and neonatal mortality will be tracked among all participants. All
      stillbirths and neonatal deaths in this population will be characterized with respect to
      cause and Rh-negativity.
Rhesus (Rh) disease is a preventable condition caused by an incompatibility between maternal
      and fetal red blood cells (RBCs). If a person's RBCs lacks a certain protein s/he is said to
      be Rh-negative. Similarly, if a person's RBCs have that same protein, s/he is said to be
      Rh-positive. If a pregnant woman's is Rh-negative and her fetus is Rh-positive, the baby is
      at risk of Rh disease. The complications associated with Rh disease include miscarriage,
      stillbirth, and neonatal death. Among surviving newborns, Rh disease can cause anemia (low
      RBCs, which can appear as feeling tired or weak or having a shortness of breath), jaundice
      (yellowing of the skin), and brain damage. If Rh-negative women are identified, there is a
      very high chance that Rh disease of the newborn can be prevented.

      The purpose of this study is to demonstrate the feasibility of point-of-care identification
      of Rh-negative women in Dadu district, Pakistan. Determining the Rh status of pregnant women
      is the first step towards prevention of Rh disease of the newborn. By collecting information
      about a) the Rh status and blood type of pregnant women; b) the acceptability of a point of
      care test blood test of Rh disease; and, c) the acceptability of treatment for Rh negativity
      in pregnant women, the investigators will be able to improve antenatal care and prevent Rh
      disease of the newborn in rural settings. The implementation of a point-of-care Rh test will
      allow us for the identification of Rh-negative women, prompt provision of treatment, and
      prevention of Rh disease of the newborn in rural settings in Pakistan.

      As part of this study, participants will be asked a series of questions to assess
      reproductive history of pregnant women and other demographic characteristics (i.e. questions
      about home environment and lifestyle). The investigators will also ask whether they are
      willing to provide a drop of blood, collected via finger prick, to allow us to determine your
      Rh status by ELDONCARD. If Rh test reveals that the pregnant women are Rh negative, the
      investigators will offer them up to two doses of treatment, first at approximately 28 weeks
      of gestation and again within 72 hours of delivery. The injections will be administered at
      the health facility. They will also be asked to undergo an ultrasound procedure by a trained
      technician at health facility. Moreover, after the newborn is delivered, the investigators
      will also ask a series of question and perform an in-person assessment of newborn to assess
      their health within 72 hours of delivery and then again on their 29th day of life. If they
      are found to be Rh-negative and they have a miscarriage, stillbirth, or baby dies within the
      first month of life, the investigators will ask them if we can collect a sample of their
      blood for further testing.

      The investigators will conduct a prospective cohort study in Tehsil Headquarter Hospital
      (THQ) and District Headquarter Hospital (DHQ) that are situated in Dadu District, Sindh,
      Pakistan. In total, between 3 and 5 Lady Health Visitors (LHVs) will be enrolled at the study
      THQ and DHQ to administer the point-of-care test and if necessary, prophylaxis. Over the
      course of the study period, approximately 2000 pregnant women will be enrolled in total
      (across both study sites); liveborn newborns delivered to enrolled pregnant women will be
      followed for the first month of life. The sample size of 2000 pregnant women in this study is
      driven by the estimated prevalence of Rh negativity in the population (7%) and hence, the
      number of women investigators expect to offer two injections of RhIg (n=140). A sample size
      of 140 participants will enable us to measure the acceptance RhIg by pregnant women.

      This prospective cohort will include two groups of participants: a) between 3 and 5 LHVs who
      are full time employees at THQ Johi and DHQ Dadu and, b) 2000 pregnant women from the
      communities in the catchment area of THQ Johi and DHQ Dadu.

      To address one of our study aims, a single questionnaire will be administered to a cadre of
      approximately 30 health professionals (i.e., physicians, lady health visitors, nurses, etc.)
      who are not otherwise engaged in study activities.
observational model: Cohort
time perspective: Prospective
measure: Proportion of pregnant women who will accept the point of care ELDONCARD test
time frame: 12 months
description: Acceptability of the point-of-care test will be represented as the proportion of positive (i.e., Yes) responses to each of the 6 questions listed below. The acceptability of the test between sites will be compared.
Did the participant agree to have the point-of-care test?
Do you think that having the point-of-care test will provide information that could improve the health of your newborn?
Do you think the point-of-care test was safe?
Did your family approve of you having the point-of-care test?
Would you recommend the point of care test to other mothers in the village?
In the future, would you agree to have this point of care test again?
measure: Prevalence of Rhesus negativity in pregnant women
time frame: 12 months
description: Prevalence of Rhesus negativity will be calculated from the total sample size of pregnant women (2000) for the study and the total number of Rhesus-negative women (0-2000) actually identified during the study.
measure: Proportion of lady health visitors who will correctly perform point-of-care test and interpret the results of the point-of-care test
time frame: 12 months
description: Ability of each lady health visitor to perform point-of-care test, each time a test is performed, a composite score (0-16) will be generated that takes into account all 16 steps of the standardized operational protocol. Composite test scores (0-16) will be plotted over time, where time will be evaluated in increments of days, weeks, and months.
measure: Proportion of positive responses on knowledge pertaining to Rhesus disease in pregnant women and lady health visitors
time frame: 12 months
description: Knowledge uptake will be assessed in both pregnant women and lady health visitors by comparing their baseline assessments with those completed at the close of the study (proportion of positive (i.e., Yes) responses).
measure: Proportion of pregnant women who will accept RhIg prophylaxis
time frame: 12 months
description: Acceptability of RhIg prophylaxis will be represented as the proportion of positive (i.e., Yes) responses to each of the 6 questions listed below. The acceptability of RhIg prophylaxis between sites will be compared.
Did the participant verbally agree to receive prophylaxis?
Do you think that receiving prophylaxis may improve the health of your newborn?
Do you think that receiving prophylaxis was safe?
Did your family approve of you receiving prophylaxis?
Would you recommend receiving prophylaxis to other Rhesus-negative mothers in the village?
In future pregnancies, would you agree to receive more injections of RhIg prophylaxis? We will also report the proportion of participants who agreed to receive 1 and/or 2 doses of RhIg in total, and by site.
measure: Rate of stillbirths and neonatal deaths per 1000 live births in this population with respect to cause and Rhesus-negativity
time frame: 13 months
description: Rate of stillbirths and newborn deaths will be tracked throughout the study and rates will be presented per 1000 live births. Finally, we will also report mean and median antibody titers for all Rhesus-negative women who have a miscarriage, stillbirth, or their newborns die within the first month of life.
arm group label: Pregnant Women
description: 2000 pregnant women from the communities in the catchment area of THQ Johi and DHQ Dadu. Rh negative women will receive two RhIg prophylaxis injections.
arm group label: Lady Health Visitors (LHVs)
description: 3-5 LHVs who are full time employees at THQ Johi and DHQ Dadu. LHVs will perform ELDONCARD test and provide RhIg prophylaxis injections.
intervention type: Drug
intervention name: RhIg prophylaxis
description: Two RhIg prophylaxis injections for Rh negative women
arm group label: Lady Health Visitors (LHVs)
arm group label: Pregnant Women
other name: Training on Rh disease
intervention type: Device
intervention name: ELDONCARD
description: ELDONCARD point-of-care test.
arm group label: Lady Health Visitors (LHVs)
arm group label: Pregnant Women
intervention type: Diagnostic Test
intervention name: ELDONCARD Test
description: LHVs will perform ELDONCARD test.
arm group label: Lady Health Visitors (LHVs)
arm group label: Pregnant Women
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
minimum age: 15 Years
maximum age: 49 Years
last name: Sajid B Soofi, FCPS
role: Principal Investigator
affiliation: Aga Khan University
last name: Gul N Khan, MPH
role: Study Director
affiliation: Aga Khan University
last name: Shaun Morris, MPH
role: Principal Investigator
affiliation: Hospital for Sick-kids Canada
last name: Shabina Ariff, FCPS
role: Principal Investigator
affiliation: Aga Khan University
last name: Sidrah Nausheen, FCPS
role: Principal Investigator
affiliation: Aga Khan University
last name: Lisa Pell, PhD
role: Principal Investigator
affiliation: Hospital for Sick-kids Canada
last name: Alvin Zipursky, MD
role: Principal Investigator
affiliation: Eldon Biologicals A/S
facility: 
country: Pakistan
citation: Zipursky A, Bhutani VK. Impact of Rhesus disease on the global problem of bilirubin-induced neurologic dysfunction. Semin Fetal Neonatal Med. 2015 Feb;20(1):2-5. doi: 10.1016/j.siny.2014.12.001. Epub 2015 Jan 9.
PMID: 25582277
citation: Fung Kee Fung K, Eason E, Crane J, Armson A, De La Ronde S, Farine D, Keenan-Lindsay L, Leduc L, Reid GJ, Aerde JV, Wilson RD, Davies G, Desilets VA, Summers A, Wyatt P, Young DC; Maternal-Fetal Medicine Committee, Genetics Committee. Prevention of Rh alloimmunization. J Obstet Gynaecol Can. 2003 Sep;25(9):765-73. doi: 10.1016/s1701-2163(16)31006-4.
PMID: 12970812
citation: ELDON K. Simultaneous ABO and Rh groupings on cards in the laboratory or at the bedside. Dan Med Bull. 1955 Mar;2(2):33-40. No abstract available.
PMID: 14379729
citation: Biologicals, E. Clinical Evidence - Comparative Study of EldonCards. 2012
citation: Zipursky A, Paul VK. The global burden of Rh disease. Arch Dis Child Fetal Neonatal Ed. 2011 Mar;96(2):F84-5. doi: 10.1136/adc.2009.181172. Epub 2010 Oct 30. No abstract available.
PMID: 21037283
citation: World Health Organization, U., Handbook IMCI. Integrated Management of Childhood Illness. 2005.
responsible party type: Principal Investigator
investigator affiliation: Aga Khan University
investigator full name: Dr Sajid Bashir Soofi
investigator title: Associate Professor
sharing ipd: No
ipd description: There is not a plan to make individual participant data available.