<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/NCT02218151</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00051024</org_study_id>
    <secondary_id>R01CA203950-03</secondary_id>
    <nct_id>NCT02218151</nct_id>
  </id_info>
  <brief_title>Medical Home Care for Hematopoietic Stem Cell Transplantation Phase 2</brief_title>
  <official_title>Patient-Centered Medical Home Care for Hematopoietic Stem Cell Transplantation: A Randomized Phase 2 Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hematopoietic stem cell transplantation (HCT) has the potential to cure a variety of&#xD;
      malignant and non-malignant diseases. However, it is associated with significant morbidity,&#xD;
      and treatment-related mortality. This is due in large part to the prolonged pancytopenia and&#xD;
      immunosuppression associated with the preparatory regimen of chemotherapy and/or radiation&#xD;
      and the wait until engraftment of the transplanted hematopoietic stem cells. During this&#xD;
      vulnerable period, infectious complications are common. Historically HCT patients were kept&#xD;
      in protected environments to safeguard their health during the pancytopenic phase; despite&#xD;
      these measures, infectious complications and graft versus host disease (GVHD) remained common&#xD;
      and lead to significant morbidity and mortality after HCT. Currently patients are still&#xD;
      closely watched in the inpatient or day hospital environment, though recent practices allow&#xD;
      patients more freedom. This study randomizes eligible patients to receive post-transplant&#xD;
      care at home vs. in the hospital or clinic, per standard of care. The primary objective is to&#xD;
      compare the incidence of grade II-IV acute GVHD at 6 months in patients receiving&#xD;
      patient-centered medical home (PCMH) vs standard care.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The patient-centered medical home (PCMH) is an exciting strategy that has the potential to&#xD;
      revolutionize hematopoietic stem cell transplantation (HCT). Traditionally, home care has&#xD;
      been used for palliative care in end-stage cancer patients and in geriatrics. More recently&#xD;
      the PCMH has gained increasing adoption for both primary care and care of medically complex&#xD;
      patients. The core of the PCMH lies in the interaction between the healthcare team, the&#xD;
      patient's family and support, and above all, the patient. These interactions can be enhanced&#xD;
      through health information technologies such as the electronic health record (EHR) and&#xD;
      videoconferencing via iPads. In addition, collection of patient reported outcomes (PRO) will&#xD;
      allow feedback and adjustments.&#xD;
&#xD;
      This integration is especially important when considering the multiple complicated needs of&#xD;
      the HCT patient: navigating a Byzantine healthcare system that often requires input and&#xD;
      coordination from multiple specialists including transplanters, hematologists, infectious&#xD;
      disease physicians, gastroenterologists, psychiatrists, nutritionists, pharmacists, social&#xD;
      workers, financial coordinators, etc.; managing medication regimens to prevent infections,&#xD;
      GVHD, and other complications (not to mention avoiding drug and food interactions); adjusting&#xD;
      to multiple side effects including fatigue, weakness, anorexia, nausea, vomiting, diarrhea,&#xD;
      rashes, pain, anxiety, stress, organ failure, etc.; the sheer amount of time required for&#xD;
      healthcare visits, lab draws, waiting for results, infusions, transfusions, etc.; physical&#xD;
      and psychosocial struggles of living with a life-threatening disease; and the burdens of a&#xD;
      treatment that often seems as debilitating as the disease. The PCMH provides&#xD;
      patient-centered, comprehensive, accessible, and coordinated care and a systems-based&#xD;
      approach to quality and safety: these attributes are essential to the successful care of the&#xD;
      complicated HCT patient. this approach has the potential to lower overall costs while&#xD;
      preserving or increasing the quality of care.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low accrual due to covid-19 and resulting staffing shortages&#xD;
  </why_stopped>
  <start_date type="Actual">September 3, 2014</start_date>
  <completion_date type="Actual">February 14, 2022</completion_date>
  <primary_completion_date type="Actual">July 12, 2021</primary_completion_date>
  <phase>N/A</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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Acute Graft Versus Host Disease (aGVHD)</measure>
    <time_frame>6 months</time_frame>
    <description>The primary endpoint is the incidence (number of events) of grade II-IV acute GVHD at 6 months. GVHD will be evaluated daily by advanced practice providers (APPs) according to standard criteria. The investigators will compare GVHD incidence rates between treatment arms using survival type regression modeling that takes competing risks into account. They will examine cause-specific Cox proportional hazards models as well as the proportional subdistribution hazard regression model developed by Fine and Gray. While the primary treatment comparison will be unadjusted, adjustment for covariates to explore the impact of various risk factors will also be performed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of Infection</measure>
    <time_frame>1 year</time_frame>
    <description>Rates of bacterial, fungal, and viral infections as well as overall infections at one year.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Free Survival (DFS)</measure>
    <time_frame>1 year</time_frame>
    <description>Disease free survival at one year.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>1 year</time_frame>
    <description>Overall survival at one year.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Comparison of Gut Microbiota</measure>
    <time_frame>6 months</time_frame>
    <description>Shannon diversity index will be compared using unpaired two-sided Student's t tests with a more stringent cut-off of 0.0125 given multiple comparisons, by the Bonferroni correction for 4 time periods of independent comparisons. Comparisons of bacterial populations will be made by using the Adonis non-parametric method from within the Qiime package using UnifFrac distance matrices from the populations being compared. P values will be calculated with α= 0.05. Metastatistics will be used for further statistical analyses of population structure, membership, and diversity with metadata such as time from transplant and dietary measurements such as caloric intake. Changes in specific bacterial families of interest will be compared using a two-sided Student's t test, with normality confirmed by D'Agostino and Pearson omnibus test with p≤0.05. All other comparisons will be done using two-sided Mann-Whitney tests.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Blood Disorders</condition>
  <arm_group>
    <arm_group_label>Patient-Centered Medical Home (PCMH)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Day-to-Day Care:&#xD;
Advanced Practice Providers (APP) will travel to subjects' homes in the morning, where they will perform the same daily assessment as standard care. They will draw labs and bring them back to the hospital for processing. When results are available, a second home visit is made to deliver necessary interventions. Subjects will have internet access through cellular-networked iPads and have daily videoconferences with their physicians. Daily follow up at home will continue until discharge as per above criteria.&#xD;
Caregivers: identified by the subject as the person taking primary care of them will answer surveys and also collect stool samples to analyze in conjunction with those from subjects.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>These subjects will begin as inpatients or outpatients, where advanced practice providers (APPs) (nurse practitioners and physician assistants) will perform histories and physical exams. Nurses will collect labs and providers will enter orders in our electronic health record (EHR). All steps will be repeated daily until discharge to home. Suitability for discharge is determined by standard clinical criteria including stable blood counts, freedom from active or severe complications (e.g. active infection, severe GVHD), and ability to care for self.&#xD;
Caregivers: identified by the subject as the person taking primary care of them will answer surveys and also collect stool samples to analyze in conjunction with those from subjects.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Patient-Centered Medical Home (PCMH)</intervention_name>
    <description>Subjects will receive their conditioning chemotherapy +/- radiation and stem cells in the hospital or day hospital, after which they will receive care during the neutropenic/recovery period at home. Advanced Practice Providers (APP) will travel to subjects' homes in the morning, where they will perform the same daily assessment as standard care. They will draw labs and bring them back to the hospital for processing. When results are available, a second home visit is made to deliver necessary interventions. Subjects will have internet access through cellular-networked iPads and have daily videoconferences with their physicians. Daily follow up at home will continue until discharge as per above criteria.</description>
    <arm_group_label>Patient-Centered Medical Home (PCMH)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard Care</intervention_name>
    <description>Subjects will receive their conditioning chemotherapy +/- radiation and stem cells in the hospital or day hospital, after which they will receive care during the neutropenic/recovery period inpatient or outpatient. Advanced practice providers (APPs) will perform histories and physical exams. Nurses will collect labs and inpatient rounds occur twice daily, or for outpatients receiving care through our outpatient clinics, a healthcare provider typically sees them daily for the first month following transplant or discharge from the day hospital.</description>
    <arm_group_label>Standard Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Scheduled to undergo a hematopoietic stem cell transplant for any cancer or non-cancer&#xD;
             illness&#xD;
&#xD;
          2. Age 18-80 years of age&#xD;
&#xD;
          3. Karnofsky Performance Scale (KPS)&gt; 80&#xD;
&#xD;
          4. A home that is deemed, upon inspection, in suitable condition to serve as a medical&#xD;
             home, within a 90-minute driving distance of Duke&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Lack of a caregiver&#xD;
&#xD;
          2. Pregnant women&#xD;
&#xD;
          3. Patients with a documented active infection prior to starting their preparative&#xD;
             regimen. This includes grade 3 or higher viral, bacterial, or fungal infection.&#xD;
&#xD;
          4. Use of homeopathic medications or probiotics that may impact gut microbiota&#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>Nelson J C, MD, MBA</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Adult Bone Marrow Transplant Clinic</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <last_update_submitted>August 17, 2023</last_update_submitted>
  <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hematopoietic</keyword>
  <keyword>Stem Cell</keyword>
  <keyword>Transplant</keyword>
  <keyword>patient-centered</keyword>
  <keyword>Microbiota</keyword>
  <keyword>GVHD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hematologic Diseases</mesh_term>
  </condition_browse>
  <!-- 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/NCT02218151
org study id: Pro00051024
secondary id: R01CA203950-03
nct id: NCT02218151
lead sponsor: 
has dmc: Yes
Hematopoietic stem cell transplantation (HCT) has the potential to cure a variety of
      malignant and non-malignant diseases. However, it is associated with significant morbidity,
      and treatment-related mortality. This is due in large part to the prolonged pancytopenia and
      immunosuppression associated with the preparatory regimen of chemotherapy and/or radiation
      and the wait until engraftment of the transplanted hematopoietic stem cells. During this
      vulnerable period, infectious complications are common. Historically HCT patients were kept
      in protected environments to safeguard their health during the pancytopenic phase; despite
      these measures, infectious complications and graft versus host disease (GVHD) remained common
      and lead to significant morbidity and mortality after HCT. Currently patients are still
      closely watched in the inpatient or day hospital environment, though recent practices allow
      patients more freedom. This study randomizes eligible patients to receive post-transplant
      care at home vs. in the hospital or clinic, per standard of care. The primary objective is to
      compare the incidence of grade II-IV acute GVHD at 6 months in patients receiving
      patient-centered medical home (PCMH) vs standard care.
The patient-centered medical home (PCMH) is an exciting strategy that has the potential to
      revolutionize hematopoietic stem cell transplantation (HCT). Traditionally, home care has
      been used for palliative care in end-stage cancer patients and in geriatrics. More recently
      the PCMH has gained increasing adoption for both primary care and care of medically complex
      patients. The core of the PCMH lies in the interaction between the healthcare team, the
      patient's family and support, and above all, the patient. These interactions can be enhanced
      through health information technologies such as the electronic health record (EHR) and
      videoconferencing via iPads. In addition, collection of patient reported outcomes (PRO) will
      allow feedback and adjustments.

      This integration is especially important when considering the multiple complicated needs of
      the HCT patient: navigating a Byzantine healthcare system that often requires input and
      coordination from multiple specialists including transplanters, hematologists, infectious
      disease physicians, gastroenterologists, psychiatrists, nutritionists, pharmacists, social
      workers, financial coordinators, etc.; managing medication regimens to prevent infections,
      GVHD, and other complications (not to mention avoiding drug and food interactions); adjusting
      to multiple side effects including fatigue, weakness, anorexia, nausea, vomiting, diarrhea,
      rashes, pain, anxiety, stress, organ failure, etc.; the sheer amount of time required for
      healthcare visits, lab draws, waiting for results, infusions, transfusions, etc.; physical
      and psychosocial struggles of living with a life-threatening disease; and the burdens of a
      treatment that often seems as debilitating as the disease. The PCMH provides
      patient-centered, comprehensive, accessible, and coordinated care and a systems-based
      approach to quality and safety: these attributes are essential to the successful care of the
      complicated HCT patient. this approach has the potential to lower overall costs while
      preserving or increasing the quality of care.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Acute Graft Versus Host Disease (aGVHD)
time frame: 6 months
description: The primary endpoint is the incidence (number of events) of grade II-IV acute GVHD at 6 months. GVHD will be evaluated daily by advanced practice providers (APPs) according to standard criteria. The investigators will compare GVHD incidence rates between treatment arms using survival type regression modeling that takes competing risks into account. They will examine cause-specific Cox proportional hazards models as well as the proportional subdistribution hazard regression model developed by Fine and Gray. While the primary treatment comparison will be unadjusted, adjustment for covariates to explore the impact of various risk factors will also be performed.
measure: Rate of Infection
time frame: 1 year
description: Rates of bacterial, fungal, and viral infections as well as overall infections at one year.
measure: Disease Free Survival (DFS)
time frame: 1 year
description: Disease free survival at one year.
measure: Overall Survival
time frame: 1 year
description: Overall survival at one year.
measure: Comparison of Gut Microbiota
time frame: 6 months
description: Shannon diversity index will be compared using unpaired two-sided Student's t tests with a more stringent cut-off of 0.0125 given multiple comparisons, by the Bonferroni correction for 4 time periods of independent comparisons. Comparisons of bacterial populations will be made by using the Adonis non-parametric method from within the Qiime package using UnifFrac distance matrices from the populations being compared. P values will be calculated with α= 0.05. Metastatistics will be used for further statistical analyses of population structure, membership, and diversity with metadata such as time from transplant and dietary measurements such as caloric intake. Changes in specific bacterial families of interest will be compared using a two-sided Student's t test, with normality confirmed by D'Agostino and Pearson omnibus test with p≤0.05. All other comparisons will be done using two-sided Mann-Whitney tests.
arm group label: Patient-Centered Medical Home (PCMH)
arm group type: Experimental
description: Day-to-Day Care:
Advanced Practice Providers (APP) will travel to subjects' homes in the morning, where they will perform the same daily assessment as standard care. They will draw labs and bring them back to the hospital for processing. When results are available, a second home visit is made to deliver necessary interventions. Subjects will have internet access through cellular-networked iPads and have daily videoconferences with their physicians. Daily follow up at home will continue until discharge as per above criteria.
Caregivers: identified by the subject as the person taking primary care of them will answer surveys and also collect stool samples to analyze in conjunction with those from subjects.
arm group label: Standard Care
arm group type: Active Comparator
description: These subjects will begin as inpatients or outpatients, where advanced practice providers (APPs) (nurse practitioners and physician assistants) will perform histories and physical exams. Nurses will collect labs and providers will enter orders in our electronic health record (EHR). All steps will be repeated daily until discharge to home. Suitability for discharge is determined by standard clinical criteria including stable blood counts, freedom from active or severe complications (e.g. active infection, severe GVHD), and ability to care for self.
Caregivers: identified by the subject as the person taking primary care of them will answer surveys and also collect stool samples to analyze in conjunction with those from subjects.
intervention type: Other
intervention name: Patient-Centered Medical Home (PCMH)
description: Subjects will receive their conditioning chemotherapy +/- radiation and stem cells in the hospital or day hospital, after which they will receive care during the neutropenic/recovery period at home. Advanced Practice Providers (APP) will travel to subjects' homes in the morning, where they will perform the same daily assessment as standard care. They will draw labs and bring them back to the hospital for processing. When results are available, a second home visit is made to deliver necessary interventions. Subjects will have internet access through cellular-networked iPads and have daily videoconferences with their physicians. Daily follow up at home will continue until discharge as per above criteria.
arm group label: Patient-Centered Medical Home (PCMH)
intervention type: Other
intervention name: Standard Care
description: Subjects will receive their conditioning chemotherapy +/- radiation and stem cells in the hospital or day hospital, after which they will receive care during the neutropenic/recovery period inpatient or outpatient. Advanced practice providers (APPs) will perform histories and physical exams. Nurses will collect labs and inpatient rounds occur twice daily, or for outpatients receiving care through our outpatient clinics, a healthcare provider typically sees them daily for the first month following transplant or discharge from the day hospital.
arm group label: Standard Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nelson J C, MD, MBA
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hematologic Diseases