<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/NCT03009526</url>
  </required_header>
  <id_info>
    <org_study_id>MAC-P.02/16/1872</org_study_id>
    <nct_id>NCT03009526</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of IPTp-DP Versus IPTp-SP in Malawi</brief_title>
  <acronym>STOPMIP-MW</acronym>
  <official_title>A Prospective Randomized Open-Label Study on the Efficacy and Safety of Intermittent Preventive Treatment in Pregnancy (IPTp) With Dihydroartemisinin-Piperaquine (DP) Versus IPTp With Sulfadoxine-Pyrimethamine (SP) in Malawi</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kamuzu University of Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Centers for Disease Control and Prevention</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Kamuzu University of Health Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to compare the efficacy of monthly IPTp-DP with monthly IPTp-SP to determine&#xD;
      if IPTp-DP is associated with a reduction in malaria infection at delivery among HIV-negative&#xD;
      women in an area with high levels of SP resistance in Malawi.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Problem to be studied Malaria in pregnancy (MiP) due to Plasmodium falciparum infection is a&#xD;
      major cause of maternal morbidity and poor birth outcomes in malaria-endemic countries.&#xD;
      Pregnant women are at increased risk of more frequent and severe malaria infections than&#xD;
      non-pregnant women. Intermittent preventive treatment in pregnancy (IPTp) with&#xD;
      sulfadoxine-pyrimethamine (SP), which involves administration of treatment doses of SP at&#xD;
      each antenatal visit in the second and third trimesters of pregnancy, at least one month&#xD;
      apart, irrespective of malaria parasitemia, is currently recommended for all women, except&#xD;
      HIV positive women taking daily cotrimoxazole prophylaxis, in areas with stable moderate to&#xD;
      high transmission of malaria.&#xD;
&#xD;
      SP is the only drug currently used for IPTp. Due to increasing resistance to SP, it is no&#xD;
      longer used as a treatment for symptomatic malaria, however, IPTp-SP remains effective even&#xD;
      in areas where SP resistance in children under five (determined by in vivo efficacy studies)&#xD;
      is up to 26%, and continues to be used for IPTp in countries where SP is no longer&#xD;
      recommended to treat symptomatic malaria. However, IPTp-SP has become more controversial&#xD;
      given recent data from northern Tanzania and Malawi that have demonstrated that at higher&#xD;
      rates of resistance, IPTp-SP may no longer be effective.&#xD;
&#xD;
      Alternative drugs which could replace SP have been tested; mefloquine,&#xD;
      azithromycin-chloroquine, and amodiaquine have been abandoned as options due to poor&#xD;
      tolerability among pregnant women. Dihydroartemisinin-Piperaquine (DP) remains an attractive&#xD;
      option because of the long half-life of piperaquine (PQ) and the demonstrated efficacy,&#xD;
      safety, and tolerability in pregnancy. Recent studies in Kenya and Uganda using DP for IPTp&#xD;
      demonstrated a significant reduction in the prevalence of malaria throughout pregnancy and at&#xD;
      the time of delivery. However, there was not a clear benefit in terms of improved neonatal&#xD;
      outcomes. Additional studies are therefore needed to determine the impact of switching from&#xD;
      IPTp-SP to IPTp-DP.&#xD;
&#xD;
      Study aims Primary objectives To compare the efficacy of monthly IPTp-DP with monthly IPTp-SP&#xD;
      to determine if IPTp-DP is associated with a reduction in malaria infection at delivery among&#xD;
      HIV-negative women in an area with high levels of SP resistance in Malawi.&#xD;
&#xD;
      Secondary objectives&#xD;
&#xD;
        -  To determine if IPTp-DP results in decreased fetal morbidity compared with IPTp-SP,&#xD;
           where fetal morbidity is defined as the composite of any of the following: Preterm birth&#xD;
           (&lt; 37 weeks gestation), low birth weight (LBW) (&lt; 2,500 grams), or small for gestational&#xD;
           age (SGA).&#xD;
&#xD;
        -  To evaluate the tolerability and safety of IPTp-DP in the second and third trimesters of&#xD;
           pregnancy, including an assessment of cardiac risk, as measured by changes in QTc&#xD;
           intervals from baseline with each successive dose.&#xD;
&#xD;
        -  To compare the frequency of adverse events and fetal congenital malformations in IPTp-DP&#xD;
           with IPTp-SP.&#xD;
&#xD;
        -  To assess how SP and DP affect the maternal intestinal and vaginal microbiome.&#xD;
&#xD;
      Methodology Open-label, 2 arm randomized controlled superiority trial to compare the efficacy&#xD;
      and safety of IPTp-DP to IPTp-SP in Malawi. The trial is designed to show a 60% decrease in&#xD;
      malaria infection at delivery among HIV-negative women of all gravidity when IPTp-DP is used&#xD;
      instead of IPTp-SP.&#xD;
&#xD;
      Expected findings and dissemination It is expected that in areas of high SP resistance,&#xD;
      IPTp-DP will be superior to IPTp-SP in decreasing malaria infection at delivery. In addition,&#xD;
      it is anticipated that DP will be well-tolerated among pregnant women and that fetal outcomes&#xD;
      will be better than IPTp-SP.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 17, 2017</start_date>
  <completion_date type="Actual">October 24, 2018</completion_date>
  <primary_completion_date type="Actual">October 24, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Malaria infection at the time of delivery</measure>
    <time_frame>delivery</time_frame>
    <description>The composite of peripheral and placental parasitemia, detected by placental histology, positive peripheral blood smear at the time of delivery, or positive rapid diagnostic test at the time of delivery</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fetal morbidity</measure>
    <time_frame>Delivery</time_frame>
    <description>Composite endpoint of fetal morbidity, defined as any of the following: Preterm birth (birth before 37 weeks gestation), Low-birth-weight (birth weight under 2,500 grams), Small for gestational age (SGA)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Electrocardiogram changes following the receipt of DP</measure>
    <time_frame>4-6 hours after the 3rd dose with each course</time_frame>
    <description>QTc will be measured in a subset of women 4-6 hours after the 3rd dose of each course</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiome changes following receipt of DP or SP</measure>
    <time_frame>From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months</time_frame>
    <description>We will measure the changes in the intestinal and vaginal microbiome induced by DP and SP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal hemoglobin at 3rd trimester</measure>
    <time_frame>3rd trimester</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maternal anemia at 3rd trimester</measure>
    <time_frame>3rd trimester</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fetal anemia</measure>
    <time_frame>Delivery</time_frame>
    <description>Anemia/ hemoglobin measured from cord blood</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of clinical malaria episodes</measure>
    <time_frame>From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of all cause sick visits</measure>
    <time_frame>From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious adverse events</measure>
    <time_frame>From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">602</enrollment>
  <condition>Malaria</condition>
  <condition>Pregnancy</condition>
  <arm_group>
    <arm_group_label>Sulfadoxine-pyrimethamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intermittent preventive treatment with Sulfadoxine-pyrimethamine: Monthly dose of 3 co-formulated tablets containing 500 mg sulfadoxine and 25 mg pyrimethamine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>dihydroartemisinin-piperaquine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intermittent preventive treatment with dihydroartemisinin-piperaquine: Monthly course of daily doses of co-formulated DP tablets containing 40 mg dihydroartemisinin and 320 mg piperaquine, dosed based on the woman's weight, for 3 days:&#xD;
24-35.9 kg: Two tablets&#xD;
36-59.9 kg: Three tablets&#xD;
60-79.9 kg: Four tablets&#xD;
≥80 kg: Five tablets</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sulfadoxine-pyrimethamine</intervention_name>
    <description>500 mg sulfadoxine and 25 mg pyrimethamine</description>
    <arm_group_label>Sulfadoxine-pyrimethamine</arm_group_label>
    <other_name>Fansidar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>dihydroartemisinin-piperaquine</intervention_name>
    <description>40 mg dihydroartemisinin and 320 mg piperaquine</description>
    <arm_group_label>dihydroartemisinin-piperaquine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Viable singleton pregnancy&#xD;
&#xD;
          -  Gestational age ≤28 completed weeks (28 6/7) by fundal height/ultrasound&#xD;
&#xD;
          -  Maternal age ≥16 years&#xD;
&#xD;
          -  No history of IPTp use during this pregnancy&#xD;
&#xD;
          -  Willing to participate and complete the study schedule, including laboratory studies&#xD;
             and delivery in the labor ward of the study clinic or hospital&#xD;
&#xD;
          -  Willing to sign or thumb print informed consent&#xD;
&#xD;
          -  Resident of study area and intending to stay in the area for the duration of the&#xD;
             follow-up&#xD;
&#xD;
          -  HIV-negative at enrolment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  HIV-positive or unknown&#xD;
&#xD;
          -  Multiple gestation&#xD;
&#xD;
          -  High-risk pregnancy, including any pre-existing illness likely to cause complication&#xD;
             of pregnancy (hypertension, diabetes, asthma, epilepsy, renal disease, liver disease,&#xD;
             fistula repair, leg or spine deformity)&#xD;
&#xD;
          -  Severe anemia requiring blood transfusion (Hb &lt;7.0 g/dL) at enrolment&#xD;
&#xD;
          -  Known allergy or previous adverse reaction to any of the study drugs&#xD;
&#xD;
          -  Previous inclusion in the same study&#xD;
&#xD;
          -  Participating in other malaria intervention studies&#xD;
&#xD;
          -  Known or suspected cardiac disease&#xD;
&#xD;
          -  Corrected QT interval (QTcF) greater than 450 ms at baseline&#xD;
&#xD;
          -  Patients taking any of the following drugs:&#xD;
&#xD;
               -  Antimicrobial agents of the following classes (systemic use only):&#xD;
&#xD;
                    -  Macrolides (e.g. erythromycin, clarithromycin, azithromycin, roxithromycin)&#xD;
&#xD;
                    -  Fluoroquinolones (e.g., levofloxacin, moxifloxacin, sparfloxacin)&#xD;
&#xD;
                    -  Pentamidine&#xD;
&#xD;
               -  Antiarrhythmic agents (e.g. amiodarone, sotalol)&#xD;
&#xD;
               -  Antihistamines (e.g. promethazine)&#xD;
&#xD;
               -  Antifungals (systemic): ketoconazole, fluconazole, itraconazole&#xD;
&#xD;
               -  Antiretrovirals: Saquinavir&#xD;
&#xD;
               -  Diuretics (e.g. hydrochlorothiazide, furosemide)&#xD;
&#xD;
               -  Antipsychotics (neuroleptics): haloperidol, thioridazine&#xD;
&#xD;
               -  Antidepressants: imipramine, citalopram, escitalopram&#xD;
&#xD;
               -  Antiemetics: domperidone, chlorpromazine, ondansetron&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Don P Mathanga, MBBS PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Malawi College of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Julie Gutman, MD MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centers for Disease Control and Prevention</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Malaria Alert Center, University of Malawi College of Medicine</name>
      <address>
        <city>Liwonde</city>
        <country>Malawi</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Malawi</country>
  </location_countries>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>December 13, 2016</study_first_submitted>
  <study_first_submitted_qc>December 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 4, 2017</study_first_posted>
  <last_update_submitted>July 22, 2021</last_update_submitted>
  <last_update_submitted_qc>July 22, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Kamuzu University of Health Sciences</investigator_affiliation>
    <investigator_full_name>Julie Gutman</investigator_full_name>
    <investigator_title>Medical epidemiologist</investigator_title>
  </responsible_party>
  <keyword>Malaria</keyword>
  <keyword>Pregnancy</keyword>
  <keyword>Malawi</keyword>
  <keyword>Intermittent preventive treatment</keyword>
  <keyword>dihydroartemisinin-piperaquine</keyword>
  <keyword>sulfadoxine-pyrimethamine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Malaria</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pyrimethamine</mesh_term>
    <mesh_term>Piperaquine</mesh_term>
    <mesh_term>Sulfadoxine</mesh_term>
    <mesh_term>Fanasil, pyrimethamine drug combination</mesh_term>
    <mesh_term>Artenimol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD will be shared with other researches upon submission and approval of a detailed request</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>January 2022</ipd_time_frame>
    <ipd_access_criteria>IPD will be shared with other researches upon submission and approval of a detailed request</ipd_access_criteria>
  </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/NCT03009526
org study id: MAC-P.02/16/1872
nct id: NCT03009526
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study aims to compare the efficacy of monthly IPTp-DP with monthly IPTp-SP to determine
      if IPTp-DP is associated with a reduction in malaria infection at delivery among HIV-negative
      women in an area with high levels of SP resistance in Malawi.
Problem to be studied Malaria in pregnancy (MiP) due to Plasmodium falciparum infection is a
      major cause of maternal morbidity and poor birth outcomes in malaria-endemic countries.
      Pregnant women are at increased risk of more frequent and severe malaria infections than
      non-pregnant women. Intermittent preventive treatment in pregnancy (IPTp) with
      sulfadoxine-pyrimethamine (SP), which involves administration of treatment doses of SP at
      each antenatal visit in the second and third trimesters of pregnancy, at least one month
      apart, irrespective of malaria parasitemia, is currently recommended for all women, except
      HIV positive women taking daily cotrimoxazole prophylaxis, in areas with stable moderate to
      high transmission of malaria.

      SP is the only drug currently used for IPTp. Due to increasing resistance to SP, it is no
      longer used as a treatment for symptomatic malaria, however, IPTp-SP remains effective even
      in areas where SP resistance in children under five (determined by in vivo efficacy studies)
      is up to 26%, and continues to be used for IPTp in countries where SP is no longer
      recommended to treat symptomatic malaria. However, IPTp-SP has become more controversial
      given recent data from northern Tanzania and Malawi that have demonstrated that at higher
      rates of resistance, IPTp-SP may no longer be effective.

      Alternative drugs which could replace SP have been tested; mefloquine,
      azithromycin-chloroquine, and amodiaquine have been abandoned as options due to poor
      tolerability among pregnant women. Dihydroartemisinin-Piperaquine (DP) remains an attractive
      option because of the long half-life of piperaquine (PQ) and the demonstrated efficacy,
      safety, and tolerability in pregnancy. Recent studies in Kenya and Uganda using DP for IPTp
      demonstrated a significant reduction in the prevalence of malaria throughout pregnancy and at
      the time of delivery. However, there was not a clear benefit in terms of improved neonatal
      outcomes. Additional studies are therefore needed to determine the impact of switching from
      IPTp-SP to IPTp-DP.

      Study aims Primary objectives To compare the efficacy of monthly IPTp-DP with monthly IPTp-SP
      to determine if IPTp-DP is associated with a reduction in malaria infection at delivery among
      HIV-negative women in an area with high levels of SP resistance in Malawi.

      Secondary objectives

        -  To determine if IPTp-DP results in decreased fetal morbidity compared with IPTp-SP,
           where fetal morbidity is defined as the composite of any of the following: Preterm birth
           (< 37 weeks gestation), low birth weight (LBW) (< 2,500 grams), or small for gestational
           age (SGA).

        -  To evaluate the tolerability and safety of IPTp-DP in the second and third trimesters of
           pregnancy, including an assessment of cardiac risk, as measured by changes in QTc
           intervals from baseline with each successive dose.

        -  To compare the frequency of adverse events and fetal congenital malformations in IPTp-DP
           with IPTp-SP.

        -  To assess how SP and DP affect the maternal intestinal and vaginal microbiome.

      Methodology Open-label, 2 arm randomized controlled superiority trial to compare the efficacy
      and safety of IPTp-DP to IPTp-SP in Malawi. The trial is designed to show a 60% decrease in
      malaria infection at delivery among HIV-negative women of all gravidity when IPTp-DP is used
      instead of IPTp-SP.

      Expected findings and dissemination It is expected that in areas of high SP resistance,
      IPTp-DP will be superior to IPTp-SP in decreasing malaria infection at delivery. In addition,
      it is anticipated that DP will be well-tolerated among pregnant women and that fetal outcomes
      will be better than IPTp-SP.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Malaria infection at the time of delivery
time frame: delivery
description: The composite of peripheral and placental parasitemia, detected by placental histology, positive peripheral blood smear at the time of delivery, or positive rapid diagnostic test at the time of delivery
measure: Fetal morbidity
time frame: Delivery
description: Composite endpoint of fetal morbidity, defined as any of the following: Preterm birth (birth before 37 weeks gestation), Low-birth-weight (birth weight under 2,500 grams), Small for gestational age (SGA)
measure: Electrocardiogram changes following the receipt of DP
time frame: 4-6 hours after the 3rd dose with each course
description: QTc will be measured in a subset of women 4-6 hours after the 3rd dose of each course
measure: Microbiome changes following receipt of DP or SP
time frame: From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months
description: We will measure the changes in the intestinal and vaginal microbiome induced by DP and SP
measure: Maternal hemoglobin at 3rd trimester
time frame: 3rd trimester
measure: Maternal anemia at 3rd trimester
time frame: 3rd trimester
measure: Fetal anemia
time frame: Delivery
description: Anemia/ hemoglobin measured from cord blood
measure: Incidence of clinical malaria episodes
time frame: From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months
measure: Incidence of all cause sick visits
time frame: From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months
measure: Serious adverse events
time frame: From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months
arm group label: Sulfadoxine-pyrimethamine
arm group type: Active Comparator
description: Intermittent preventive treatment with Sulfadoxine-pyrimethamine: Monthly dose of 3 co-formulated tablets containing 500 mg sulfadoxine and 25 mg pyrimethamine
arm group label: dihydroartemisinin-piperaquine
arm group type: Experimental
description: Intermittent preventive treatment with dihydroartemisinin-piperaquine: Monthly course of daily doses of co-formulated DP tablets containing 40 mg dihydroartemisinin and 320 mg piperaquine, dosed based on the woman's weight, for 3 days:
24-35.9 kg: Two tablets
36-59.9 kg: Three tablets
60-79.9 kg: Four tablets
≥80 kg: Five tablets
intervention type: Drug
intervention name: Sulfadoxine-pyrimethamine
description: 500 mg sulfadoxine and 25 mg pyrimethamine
arm group label: Sulfadoxine-pyrimethamine
other name: Fansidar
intervention type: Drug
intervention name: dihydroartemisinin-piperaquine
description: 40 mg dihydroartemisinin and 320 mg piperaquine
arm group label: dihydroartemisinin-piperaquine
criteria: 
gender: Female
minimum age: 16 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Don P Mathanga, MBBS PhD
role: Principal Investigator
affiliation: Malawi College of Medicine
last name: Julie Gutman, MD MSc
role: Principal Investigator
affiliation: Centers for Disease Control and Prevention
facility: 
country: Malawi
responsible party type: Principal Investigator
investigator affiliation: Kamuzu University of Health Sciences
investigator full name: Julie Gutman
investigator title: Medical epidemiologist
mesh term: Malaria
mesh term: Pyrimethamine
mesh term: Piperaquine
mesh term: Sulfadoxine
mesh term: Fanasil, pyrimethamine drug combination
mesh term: Artenimol
sharing ipd: Yes
ipd description: IPD will be shared with other researches upon submission and approval of a detailed request
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: January 2022
ipd access criteria: IPD will be shared with other researches upon submission and approval of a detailed request