xml: <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/NCT05982301</url>
    </required_header>
    <id_info>
      <org_study_id>FDZL-PFMG</org_study_id>
      <nct_id>NCT05982301</nct_id>
    </id_info>
    <brief_title>Sintilimab Combined With Modified FLOT Regimen in the Treatment of Metastatic Gastric Cancer</brief_title>
    <official_title>PD-1 Antibody Sintilimab Combined With Modified FLOT Regimen in the Treatment of Metastatic Gastric Cancer: a Phase II Clinical Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Fudan University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Fudan University</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 is a prospective, one-arm, single-center phase II study. The objective was to evaluate&#xD;
        the efficacy and safety of domestic PD-1 antibody Sintilimab combined with modified FLOT&#xD;
        regimen in the treatment of metastatic gastric cancer. To compare the time of maintenance of&#xD;
        treatment after induction of chemotherapy with sintilimab combined with modified FLOT regimen&#xD;
        until the reapplication of induction regimen with or without the combination of sintilimab,&#xD;
        and the time of secondary progression after signing informed consent until the reapplication&#xD;
        of induction regimen with or without the combination of sintilimab.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study set up two cohorts, Cohort A: patients with HER2-negative advanced gastric cancer,&#xD;
        and planned to enroll 87 patients with initially treated advanced gastric cancer. Thirty&#xD;
        patients with ORR of more than 70% were enrolled in the first stage and then further&#xD;
        enrolled. Cohort B: advanced gastric cancer patients with HER2 positive initial treatment,&#xD;
        the number of enrolled is not specified. Patients with initially treated advanced gastric&#xD;
        cancer who meet the inclusion criteria will be enrolled in this study to receive Sintilimab&#xD;
        combined with mFLOT regimen. Trastuzumab was given to Cohort B. The results were repeated&#xD;
        every 2 weeks and evaluated every 6 weeks. The examination methods were consistent with those&#xD;
        at baseline. Patients without disease progression were treated for a maximum of 6 cycles,&#xD;
        then switched to oral capecitabine monotherapy combined with the sintilimab until disease&#xD;
        progression, intolerable adverse reactions, patient death, or withdrawal of informed consent.&#xD;
        If intolerability toxicity of albumin paclitaxel or oxaliplatin occurs within 6 cycles,&#xD;
        maintenance is advanced to sintilimab combined with capecitabine monotherapy. Patients were&#xD;
        randomly assigned to Cohort A1 and Cohort A2 after maintaining treatment progress. Cohort A1:&#xD;
        Cohort 1 combined with mFLOT; Cohort A2: mFLOT program Therapy. The regimen was repeated&#xD;
        every 2 weeks and tumor efficacy was evaluated every 3 treatment cycles. Patients without&#xD;
        disease progression were treated for a maximum of 6 cycles before being switched to&#xD;
        monotherapy S-1 oral with or without sintilimab until disease progression, intolerable&#xD;
        adverse reactions, patient death, or withdrawal of informed consent. The treatment should&#xD;
        start within 1 week after the signing of informed consent, and the time from the signing of&#xD;
        informed consent to the first progress should be PFS1; The time from the signing of informed&#xD;
        consent to the progress of induction program back to the second progress is PFS2. In this&#xD;
        study, peripheral blood and tissue samples of patients will be collected to analyze the&#xD;
        correlation between biomarkers (such as Micro-RNA, cytokine expression levels, etc.) and&#xD;
        efficacy and prognosis. The expected time of enrollment was 48 months, and the patients were&#xD;
        observed clinically until disease progression and death. (PFS2 equals PFS1 if the induction&#xD;
        regimen is applied again after the first disease progression and the first efficacy&#xD;
        evaluation is the disease progression)&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">February 9, 2023</start_date>
    <completion_date type="Anticipated">December 2025</completion_date>
    <primary_completion_date type="Anticipated">January 2025</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Progression-Free survival 2, PFS2</measure>
      <time_frame>From date of informed consent to time of secondary progression, assessed up to 60 months</time_frame>
      <description>From date of informed consent to time of secondary progression</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall survival, OS</measure>
      <time_frame>the period from the date of randomization to the date of death from any cause, assessed up to 60 months</time_frame>
      <description>the period from the date of randomization to the date of death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective response rate</measure>
      <time_frame>Baseline, Every 6 weeks during the procedure, up to 1 year. After 1 year, every 3 months.</time_frame>
      <description>the proportion of patients whose tumor dcrease to a certain size and remained for a certain period of time, including those with complete response(CR) and partial response (PR).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-Free survival 1, PFS1</measure>
      <time_frame>From date of informed consent to time of first progression, assessed up to 60 months.</time_frame>
      <description>From date of informed consent to time of first progression</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>After Effects</measure>
      <time_frame>Baseline, Every cycle of treatment, until disease progression or death, whichever come first.</time_frame>
      <description>CTC AE Version 5.0 will be used to evaluate the clinical safety of the treatment in the study.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">87</enrollment>
    <condition>Gastric Cancer</condition>
    <condition>Chemotherapy Effect</condition>
    <condition>Immune Checkpoint Inhibitor</condition>
    <arm_group>
      <arm_group_label>Nab-POF</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Sintilimab 200mg d1 ivgtt+paclitaxel-albumin 125mg/m2 d1 ivgtt+oxaliplatin 85mg/m2 d1 ivgtt+5-FU 2.4g/m2 civ46h, q2w.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Sintilimab, paclitaxel-albumin, oxaliplatin, 5-FU</intervention_name>
      <description>The study has only one arm. Sintilimab 200mg d1 ivgtt+paclitaxel-albumin 125mg/m2 d1 ivgtt+oxaliplatin 85mg/m2 d1 ivgtt+5-FU 2.4g/m2 civ46h, q2w.</description>
      <arm_group_label>Nab-POF</arm_group_label>
      <other_name>Sintilimab+mFLOT</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Aged ≥18 years and men or women&#xD;
  &#xD;
            2. With histologically confirmed adenocarcinoma of the stomach or gastroesophageal&#xD;
               junction, local lesions that cannot be radically resected, or metastatic gastric&#xD;
               cancer&#xD;
  &#xD;
            3. For treatment-naïve patients, or postoperative recurrence at least 6 months from the&#xD;
               last adjuvant chemotherapy&#xD;
  &#xD;
            4. With Eastern Cooperative Oncology Group (ECOG) PS of 0-1&#xD;
  &#xD;
            5. With a life expectancy of more than 3 months&#xD;
  &#xD;
            6. Who obtain the following laboratory test data within 7 days (including the seventh&#xD;
               day) prior to the study screening: neutrophil count of ≥1.5 × 10^9/L, platelet count&#xD;
               of ≥100 × 10^9/L, hemoglobin level of ≥90 g/L, serum total bilirubin of ≤1.25 the&#xD;
               upper limit of normal (ULN); ALT and AST levels of ≤2.5 × ULN (≤5 × ULN for patients&#xD;
               with liver metastasis); serum creatinine level of ≤1.0 × ULN and creatinine clearance&#xD;
               of ≥50 ml/min; International Normalized ratio (INR) or prothrombin time (PT) ≤1.5 ULN;&#xD;
               If the subject is receiving anticoagulant therapy, PT should be within the prescribed&#xD;
               anticoagulant range.&#xD;
  &#xD;
            7. With at least one extragastric measurable lesion (Response Evaluation Criteria in&#xD;
               Solid Tumors [RECIST] 1.1 criteria)&#xD;
  &#xD;
            8. Patients (or their legal representative/guardian) must sign an informed consent form&#xD;
               indicating that they understand the purpose of the study, understand the procedures&#xD;
               necessary for the study, and are willing to participate in the study.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients with history of other types of cancer in the last 3 years, except for cured&#xD;
               cervical cancer or cutaneous basal cell carcinoma.&#xD;
  &#xD;
            2. Patients with symptomatic brain or leptomeningeal metastases (unless the patient has&#xD;
               been treated for &gt;2 months) who has a negative imaging result within 4 weeks before&#xD;
               participating in the study and is stable disease at study entry.&#xD;
  &#xD;
            3. Patients with clinically significant gastrointestinal obstruction, gastrointestinal&#xD;
               bleeding (defecate occult blood + + + and above) or perforation.&#xD;
  &#xD;
            4. Patients who have received PD-1, PD-L1 or PD- L2, CD137, CTLA-4 antibody therapy, or&#xD;
               any other T cells stimulate or total checkpoint pathways for specific target antibody&#xD;
               or drugs.&#xD;
  &#xD;
            5. Patients with active, or have a history and possible recurrence of autoimmune disease&#xD;
               of the subjects (such as: Systemic lupus erythematosus, rheumatoid arthritis,&#xD;
               inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis,&#xD;
               vasculitis, glomerulonephritis, etc.), or those at high risk (such as those who have&#xD;
               received an organ transplant requiring immunosuppressive therapy). However, patients&#xD;
               with vitiligo, psoriasis, alopecia, or Grave's disease who did not require systemic&#xD;
               treatment within the last 2 years, or patients with hypothyroidism who required only&#xD;
               thyroid hormone replacement therapy, and patients with type 1 diabetes who required&#xD;
               only insulin replacement therapy could be enrolled.&#xD;
  &#xD;
            6. Patients now with interstitial lung disease or pneumonia, pulmonary fibrosis, acute&#xD;
               lung diseases, radiation pneumonia.&#xD;
  &#xD;
            7. Patients who received any investigational drugs or antitumor drugs within 4 weeks&#xD;
               prior to enrollment.&#xD;
  &#xD;
            8. Patients who received immunosuppressive drugs within 4 weeks, which does not include&#xD;
               nasal, inhalation or other routes of topical corticosteroids or physiological doses of&#xD;
               systemic corticosteroids (i.e., not exceeding 10 mg/ day of prednisone or equivalent&#xD;
               doses of other corticosteroids), or short-term (not exceeding 7 days) use of&#xD;
               corticosteroids for the prevention or treatment of non-autoimmune allergic diseases.&#xD;
  &#xD;
            9. Patients who received the live attenuated vaccine within 4 weeks before the first dose&#xD;
               of study treatment. Note: Inactivated virus vaccines for injectable seasonal influenza&#xD;
               are permitted for up to 4 weeks prior to initial administration; But live attenuated&#xD;
               influenza vaccines are not allowed;&#xD;
  &#xD;
           10. Patients who received major surgery within 4 weeks before the first dose of study&#xD;
               treatment(open chest, craniotomy or laparotomy) or expected during the research and&#xD;
               treatment need to accept major surgery not associated with this study.&#xD;
  &#xD;
           11. Patients who infected with human immunodeficiency virus (HIV) disease (HIV antibody&#xD;
               positive), or with other acquired, congenital immunodeficiency disease, or has a&#xD;
               history of organ transplantation, or stem cell transplantation.&#xD;
  &#xD;
           12. Patients who have chronic active hepatitis B or active active hepatitis C. Hepatitis B&#xD;
               virus carriers, stable after drug treatment of hepatitis B (DNA drop degree is not&#xD;
               higher than 200 iu/mL or copy number &lt; 1000 copies/mL) and has cured patients with&#xD;
               hepatitis c (HCV RNA test negative) into the group.&#xD;
  &#xD;
           13. Patients with known active tuberculosis.&#xD;
  &#xD;
           14. Patients with severe infections before 4 weeks of fisrt dose of treatment, active&#xD;
               infection which needs oral or intravenous antibiotic therapy before 4 weeks of fisrt&#xD;
               dose of treatment.&#xD;
  &#xD;
           15. Patients with symptomatic congestive heart failure (New York heart association grade&#xD;
               II - IV) or symptomatic or poorly controlled arrhythmia.&#xD;
  &#xD;
           16. Patiemts with uncontrolled arterial blood pressure with specification treatment&#xD;
               (systolic blood pressure of greater than 160mmHg or diastolic blood pressure of&#xD;
               greater than 100 mmHg).&#xD;
  &#xD;
           17. Patients who had any arterial thromboembolic events, including myocardial infarction,&#xD;
               unstable angina, cerebrovascular accident, or transient ischemic attack within 6&#xD;
               months before the screening.&#xD;
  &#xD;
           18. Patinets with deep vein thrombosis, pulmonary embolism, or any other serious history&#xD;
               of thromboembolism within 3 months (implantable venous infusion port source sex or&#xD;
               catheter thrombosis, or superficial venous thrombosis were not regarded as a &quot;severe&quot;&#xD;
               thromboembolism).&#xD;
  &#xD;
           19. Patients who have a history of neurological or psychiatric disorders, such as memory,&#xD;
               epilepsy, dementia, compliance, or the peripheral nervous system disorder.&#xD;
  &#xD;
           20. alcohol dependence or 1-year history of drug or drug abuse.&#xD;
  &#xD;
           21. Pregnancy or lactation women; Those who are fertile but do not take adequate&#xD;
               contraceptive measures;&#xD;
  &#xD;
           22. may lead to the following results of other acute or chronic diseases, mental illness&#xD;
               or abnormal laboratory values: participated in or study drug dosage associated with an&#xD;
               increased risk, or interfere with the interpretation of results, and according to the&#xD;
               researcher's judgment does not conform the patient to participate in this study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>WeiJian Guo, M.D.,Ph.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fudan University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>WeiJian Guo, M.D.,Ph.D.</last_name>
      <phone>64175590</phone>
      <email>guoweijian1@hotmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>XiaoDong Zhu, M.D.,Ph.D.</last_name>
      <phone>64175590</phone>
      <email>xddr001@163.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Fudan University Shanghai Cancer Center</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200032</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Weijian Guo</last_name>
        <phone>64175590</phone>
        <email>guoweijian1@hotmail.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>May 19, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Fudan University</investigator_affiliation>
      <investigator_full_name>Weijian Guo</investigator_full_name>
      <investigator_title>Director, Head of Gastrointestinal Oncology, Principal Investigator, Clinical Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Stomach Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Paclitaxel</mesh_term>
      <mesh_term>Oxaliplatin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>We plan to share IPD after the publication of the study.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_info_type>Analytic Code</ipd_info_type>
      <ipd_time_frame>We plan to share IPD after the publication of the study.</ipd_time_frame>
      <ipd_access_criteria>Data sharing requires approval from the principal investigator.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05982301
  org study id: FDZL-PFMG
  nct id: NCT05982301
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This is a prospective, one-arm, single-center phase II study. The objective was to evaluate
        the efficacy and safety of domestic PD-1 antibody Sintilimab combined with modified FLOT
        regimen in the treatment of metastatic gastric cancer. To compare the time of maintenance of
        treatment after induction of chemotherapy with sintilimab combined with modified FLOT regimen
        until the reapplication of induction regimen with or without the combination of sintilimab,
        and the time of secondary progression after signing informed consent until the reapplication
        of induction regimen with or without the combination of sintilimab.
  This study set up two cohorts, Cohort A: patients with HER2-negative advanced gastric cancer,
        and planned to enroll 87 patients with initially treated advanced gastric cancer. Thirty
        patients with ORR of more than 70% were enrolled in the first stage and then further
        enrolled. Cohort B: advanced gastric cancer patients with HER2 positive initial treatment,
        the number of enrolled is not specified. Patients with initially treated advanced gastric
        cancer who meet the inclusion criteria will be enrolled in this study to receive Sintilimab
        combined with mFLOT regimen. Trastuzumab was given to Cohort B. The results were repeated
        every 2 weeks and evaluated every 6 weeks. The examination methods were consistent with those
        at baseline. Patients without disease progression were treated for a maximum of 6 cycles,
        then switched to oral capecitabine monotherapy combined with the sintilimab until disease
        progression, intolerable adverse reactions, patient death, or withdrawal of informed consent.
        If intolerability toxicity of albumin paclitaxel or oxaliplatin occurs within 6 cycles,
        maintenance is advanced to sintilimab combined with capecitabine monotherapy. Patients were
        randomly assigned to Cohort A1 and Cohort A2 after maintaining treatment progress. Cohort A1:
        Cohort 1 combined with mFLOT; Cohort A2: mFLOT program Therapy. The regimen was repeated
        every 2 weeks and tumor efficacy was evaluated every 3 treatment cycles. Patients without
        disease progression were treated for a maximum of 6 cycles before being switched to
        monotherapy S-1 oral with or without sintilimab until disease progression, intolerable
        adverse reactions, patient death, or withdrawal of informed consent. The treatment should
        start within 1 week after the signing of informed consent, and the time from the signing of
        informed consent to the first progress should be PFS1; The time from the signing of informed
        consent to the progress of induction program back to the second progress is PFS2. In this
        study, peripheral blood and tissue samples of patients will be collected to analyze the
        correlation between biomarkers (such as Micro-RNA, cytokine expression levels, etc.) and
        efficacy and prognosis. The expected time of enrollment was 48 months, and the patients were
        observed clinically until disease progression and death. (PFS2 equals PFS1 if the induction
        regimen is applied again after the first disease progression and the first efficacy
        evaluation is the disease progression)
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Progression-Free survival 2, PFS2
  time frame: From date of informed consent to time of secondary progression, assessed up to 60 months
  description: From date of informed consent to time of secondary progression
  measure: Overall survival, OS
  time frame: the period from the date of randomization to the date of death from any cause, assessed up to 60 months
  description: the period from the date of randomization to the date of death from any cause.
  measure: Objective response rate
  time frame: Baseline, Every 6 weeks during the procedure, up to 1 year. After 1 year, every 3 months.
  description: the proportion of patients whose tumor dcrease to a certain size and remained for a certain period of time, including those with complete response(CR) and partial response (PR).
  measure: Progression-Free survival 1, PFS1
  time frame: From date of informed consent to time of first progression, assessed up to 60 months.
  description: From date of informed consent to time of first progression
  measure: After Effects
  time frame: Baseline, Every cycle of treatment, until disease progression or death, whichever come first.
  description: CTC AE Version 5.0 will be used to evaluate the clinical safety of the treatment in the study.
  arm group label: Nab-POF
  arm group type: Experimental
  description: Sintilimab 200mg d1 ivgtt+paclitaxel-albumin 125mg/m2 d1 ivgtt+oxaliplatin 85mg/m2 d1 ivgtt+5-FU 2.4g/m2 civ46h, q2w.
  intervention type: Drug
  intervention name: Sintilimab, paclitaxel-albumin, oxaliplatin, 5-FU
  description: The study has only one arm. Sintilimab 200mg d1 ivgtt+paclitaxel-albumin 125mg/m2 d1 ivgtt+oxaliplatin 85mg/m2 d1 ivgtt+5-FU 2.4g/m2 civ46h, q2w.
  arm group label: Nab-POF
  other name: Sintilimab+mFLOT
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: WeiJian Guo, M.D.,Ph.D.
  role: Principal Investigator
  affiliation: Fudan University
  last name: WeiJian Guo, M.D.,Ph.D.
  phone: 64175590
  email: guoweijian1@hotmail.com
  last name: XiaoDong Zhu, M.D.,Ph.D.
  phone: 64175590
  email: xddr001@163.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Fudan University
  investigator full name: Weijian Guo
  investigator title: Director, Head of Gastrointestinal Oncology, Principal Investigator, Clinical Professor
  mesh term: Stomach Neoplasms
  mesh term: Paclitaxel
  mesh term: Oxaliplatin
  sharing ipd: Yes
  ipd description: We plan to share IPD after the publication of the study.
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd info type: Analytic Code
  ipd time frame: We plan to share IPD after the publication of the study.
  ipd access criteria: Data sharing requires approval from the principal investigator.