TDM: Titrated Disease Management for Patients With Hypertension

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT01390272
• Collaborator: (none)
• Enrollment: 385
• Location: 1
• Arms: 2
• Actual Duration (Months): 51.2
• Patients Per Site Per Month: 7.5

Study Details

Study Description

Brief Summary

This randomized clinical trial examines whether programs aimed at matching resources to patient hypertension (i.e. high blood pressure) control lead to greater reduction in systolic blood pressure (top number of blood pressure reading) than simply having maintenance phone calls in addition to usual care. Answering this question will provide important evidence concerning the overall goal of sustained long-term implementation of the disease management programs as part of patient aligned care teams in the Veterans Affairs and other healthcare systems.

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Behavioral: Booster/ low resource; Behavioral: Booster/ low resource; Behavioral: Medium/Level 1 resource intensity; Behavioral: High/Level 2 resource intensity	N/A

Detailed Description

Project Objectives: The investigators are conducting a two-arm 18-month randomized clinical trial for patients with pharmaceutically treated hypertension for which systolic BP is not controlled (>/=140 mmHg for non-diabetic or >/=130 mmHg for diabetic patients). The primary aim will be to compare two treatment arms/strategies in terms of impact on systolic BP control: Arm 1 - An intervention arm using titrated disease management in which patients' hypertension control, assessed at baseline, 6 and 12 months, will be used to decide the resource intensity of strategies: 1) Medium/level 1 resource intensity strategy: a registered nurse will provide monthly tailored behavioral support telephone calls + home BP monitoring; 2) High/level 2 resource intensity strategy: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management; and 3) Booster (low) resource intensity strategy: a license practice nurse (LPN) will provide bi-monthly, non-tailored behavioral support telephone calls to patients whose systolic BP comes under control. Arm 2 - A control arm, in which an LPN will provide bi-monthly non-tailored behavioral support telephone calls (same procedures as the booster (low) resource intensity strategy component of the titrated intervention).

Study Design

• Study Type: Interventional
• Actual Enrollment: 385 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Health Services Research
• Official Title: Randomized Trial of Titrated Disease Management for Patients With Hypertension
• Actual Study Start Date: Jul 27, 2012
• Actual Primary Completion Date: Oct 31, 2016
• Actual Study Completion Date: Oct 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Titration Intervention The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control.	Behavioral: Booster/ low resource; A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.; Other Names: Intervention Arm - Booster ; Behavioral: Medium/Level 1 resource intensity; Monthly tailored RN delivered calls + home BP monitoring.; Other Names: Intervention Arm - Level 1 ; Behavioral: High/Level 2 resource intensity; Pharmacist delivered telephone behavioral self-management support + Home BP monitoring with feedback to pharmacist + Algorithmic medication changes directed by pharmacist (with physician backup).; Other Names: Intervention Arm - Level 2
Active Comparator: LPN Control A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control.	Behavioral: Booster/ low resource; A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.; Other Names: Control Arm - Low resource

Outcome Measures

Primary Outcome Measures

1. Systolic Blood Pressure [Baseline]

   Continuous change in systolic blood pressure was measured as the primary outcome. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the baseline study visits.

2. Systolic Blood Pressure [6 months]

   Continuous change in systolic blood pressure was measured as the primary outcome. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the 6- month study visits.

3. Systolic Blood Pressure [12 months]

   Continuous change in systolic blood pressure was measured as the primary outcome. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the12-month study visits.

4. Systolic Blood Pressure [18 months]

   Continuous change in systolic blood pressure was measured as the primary outcome. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the18- month study visits.

Secondary Outcome Measures

1. Number of Participants With Hypertension Control [Baseline]

   The investigators examined the difference in the degree of systolic BP control over the 18 months of the study between the intervention and control arms. Control was defined as SBP < 130mmHg for hypertensive patients with diabetes and < 140mmHg for patients without diabetes. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the baseline study visit.

2. Number of Participants With Hypertension Control [6 months]

   The investigators examined the difference in the degree of systolic BP control over the 18 months of the study between the intervention and control arms. Control was defined as SBP < 130mmHg for hypertensive patients with diabetes and < 140mmHg for patients without diabetes. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the 6-month study visit.

3. Number of Participants With Hypertension Control [12 months]

   The investigators examined the difference in the degree of systolic BP control over the 18 months of the study between the intervention and control arms. Control was defined as SBP < 130mmHg for hypertensive patients with diabetes and < 140mmHg for patients without diabetes. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the 12-study visit.

4. Number of Participants With Hypertension Control [18 months]

   The investigators examined the difference in the degree of systolic BP control over the 18 months of the study between the intervention and control arms. Control was defined as SBP < 130mmHg for hypertensive patients with diabetes and < 140mmHg for patients without diabetes. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the18- month study visit.

5. Cost Effectiveness [Over 18 months of study intervention]

   One of our secondary research questions was: "If the intervention results in greater reduction in SBP than the control group, is it cost effective?" Intervention results did not show statistically significant differences between arms, therefore cost effectiveness analysis was not appropriate. While cost effectiveness was not analyzed because it was a null trial, the investigators would have used resource utilization and cost data from VA data sets to measure VA outpatient and inpatient utilization and costs by arms over 18 months. The investigators would have examined hypertension-related outpatient pharmacy prescription counts and costs in order to compare them to total outpatient pharmacy costs and the investigators would have examined inpatient utilization and costs.

6. Number of Participants Who Did Not Achieve Medication Adherence [Baseline]

   The investigators assessed adherence using patient self-report on a modified Morisky scale using 4 items: Do you ever forget to take your blood pressure medicine? Are you careless at times about taking your blood pressure medicine? When you feel better do you sometimes stop taking you blood pressure medicine? Sometimes if you feel worse when you take your blood pressure medicine, do you stop taking it? The scale is a Yes(0) or No (1) answer. A response of YES to any one of the 4 items indicated non-adherence, and responses of all no indicated adherence. The numbers in the descriptive tables reflect number non-adherent.

7. Number of Participants Who Did Not Achieve Medication Adherence [6 months]

   The investigators assessed adherence using patient self-report on a modified Morisky scale using 4 items: Do you ever forget to take your blood pressure medicine? Are you careless at times about taking your blood pressure medicine? When you feel better do you sometimes stop taking you blood pressure medicine? Sometimes if you feel worse when you take your blood pressure medicine, do you stop taking it? The scale is a Yes(0) or No (1) answer. A response of YES to any one of the 4 items indicated non-adherence, and responses of all no indicated adherence. The numbers in the descriptive tables reflect number non-adherent.

8. Number of Participants Who Did Not Achieve Medication Adherence [12 months]

   The investigators assessed adherence using patient self-report on a modified Morisky scale using 4 items: Do you ever forget to take your blood pressure medicine? Are you careless at times about taking your blood pressure medicine? When you feel better do you sometimes stop taking you blood pressure medicine? Sometimes if you feel worse when you take your blood pressure medicine, do you stop taking it? The scale is a Yes(0) or No (1) answer. A response of YES to any one of the 4 items indicated non-adherence, and responses of all no indicated adherence. The numbers in the descriptive tables reflect number non-adherent.

9. Number of Participants Who Did Not Achieve Medication Adherence [18 months]

   The investigators assessed adherence using patient self-report on a modified Morisky scale using 4 items: Do you ever forget to take your blood pressure medicine? Are you careless at times about taking your blood pressure medicine? When you feel better do you sometimes stop taking you blood pressure medicine? Sometimes if you feel worse when you take your blood pressure medicine, do you stop taking it? The scale is a Yes(0) or No (1) answer. A response of YES to any one of the 4 items indicated non-adherence, and responses of all no indicated adherence. The numbers in the descriptive tables reflect number non-adherent.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age >= 18 years.

• Assigned primary care provider in one of the clinics of the Durham VA Medical Center (VAMC) (including Community Based Outpatient Clinics for example - Hillandale Clinic and Greenville (CBOC)).

• Had at least 1 primary care visit at the Durham VA or affiliated CBOC in the last year.

• Diagnosis of hypertension requiring medication, as determined by: ICD 401.0, 401.1, or 401.9 for >= 2 outpatient encounters during the prior year and Received a prescription for at least 1 of the following classes of hypertensive medication in the previous year: 1) ACE inhibitors; 2) alpha blockers; 3) angiogenesis II inhibitors; 4) beta blockers; 5) calcium channel blockers; 6) diuretics; 7) antihypertensive combination; and/or 8) antihypertensives, other.

• Out of control systolic blood pressure: Durham VAMC (including CBOCs or other affiliated clinics captured in the Durham VAMC electronic health record) outpatient BP measurements >= 150 mmHg for non-diabetic or >= 140 mmHg for diabetic patients over the last year and last systolic BP measurement >= 140 mmHg for non-diabetic or >= 130 mmHg for diabetic patients. If additional patients need to be approached to be offered the opportunity for further screening, non-diabetic patients with mean outpatient systolic BP of >= 140 mmHg or diabetic patients with mean outpatient systolic BP of >= 130 mmHg over the past year may be approached.

Patients must indicate that they both:

• Have a VA or affiliated clinic provider that they consider to be their main PCP.

• Receive the majority of healthcare at the Durham VA Medical Center (or affiliated clinic - such as Hillandale or Greenville).

Exclusion Criteria:

• Active diagnosis of psychosis.

• Diagnosis of metastatic cancer.

• Type 1 diabetes

• Class IV congestive heart failure (CHF).

• Currently receiving kidney dialysis or if estimated glomerular filtration rate (eGFR) levels are <= 15.

• Chronic obstructive pulmonary disease (COPD) requiring oxygen.

• Resident in nursing home or receiving home healthcare.

• Patient is pregnant or reports planning to become pregnant in the next two years

• At the time of potential enrollment, participating in another ongoing hypertension, diabetes, cholesterol, or cardiovascular disease clinical trial.

• Planning to leave the area prior to the anticipated end of participation.

• Inability or unwillingness to come to the Durham VAMC or affiliated clinic such as Hillandale or Greenville for baseline-, 6-, 12-, and 18-month study visits.

• Does not have reasonable access to a telephone.

• Does not speak English.

• Severely impaired hearing or speech (Patients must be able to respond to phone calls.).

• Severely impaired vision (Patients must be able to read mailed material).

• Refusal or inability to provide informed consent and HIPAA authorization form.

• Arm size > 50 cm

• Unable to obtain (including by arm) valid blood pressure readings

• Inadequate mental status to complete the protocol, as judged by five or more errors on the Short Portable Mental Status Questionnaire (SPMSQ).

• Former, current or pending solid organ or bone marrow transplant patient.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Durham VA Medical Center, Durham, NC	Durham	North Carolina	United States	27705

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: George L Jackson, PhD MHA, Durham VA Medical Center, Durham, NC

Study Documents (Full-Text)

• Study Protocol - Mar 4, 2016
• Informed Consent Form - Aug 25, 2014

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01390272
• Other Study ID Numbers: IIR 10-383
• First Posted: Jul 11, 2011
• Last Update Posted: Feb 11, 2019
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by VA Office of Research and Development: Hypertension; Telephone; Disease Management; Veterans; Pharmacists; Nurses
• Additional relevant MeSH terms: Hypertension

Study Results

Participant Flow

Recruitment Details	The study was conducted among patients receiving primary care at the Durham VAMC, including VA Community Based Outpatient Clinics (CBOC).

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Period Title: Overall Study
STARTED	192	193
6 Month Follow up	162	171
12 Month Follow up	139	159
18 Month Follow up	155	160
COMPLETED	175	178
NOT COMPLETED	17	15

Baseline Characteristics

Arm/Group Title	Titration Intervention	LPN Control	Total
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	Total of all reporting groups
Overall Participants	192	193	385
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.2 (9.0)	62.9 (8.5)	63.5 (8.8)
Sex: Female, Male (Count of Participants)
Female	16 8.3%	13 6.7%	29 7.5%
Male	176 91.7%	180 93.3%	356 92.5%

Outcome Measures

1. Primary Outcome

Title	Systolic Blood Pressure
Description	Continuous change in systolic blood pressure was measured as the primary outcome. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the baseline study visits.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	192	193
Mean (Standard Deviation) [mmHg]	143.5 (17.7)	143.7 (17.5)

2. Primary Outcome

Title	Systolic Blood Pressure
Description	Continuous change in systolic blood pressure was measured as the primary outcome. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the 6- month study visits.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

30 out of the 192 participants in the Titration Intervention group and 22 out of the 193 in the LPN control group had missing blood pressure measurement at 6 months due to not completing the assessment. One additional participant in the LPN control had missing blood pressure measurement at 6 months due to not being able to get a reading.

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	162	171
Mean (Standard Deviation) [mmHg]	137.1 (17.7)	140.3 (18.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Titration Intervention, LPN Control
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Mixed Models Analysis
	Comments	Constrained longitudinal model adjusting for baseline stratification variables of diabetes status and blood pressure control.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -5.9 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Systolic Blood Pressure
Description	Continuous change in systolic blood pressure was measured as the primary outcome. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the12-month study visits.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Analysis Population Description: Analysis Population Description: 53 out of the 192 participants in the Titration Intervention group and 34 out of the 193 in the LPN control group had missing blood pressure measurement at 12 months due to not completing the assessment.

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	139	159
Mean (Standard Deviation) [mmHg]	135.9 (15.7)	138.4 (17.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Titration Intervention, LPN Control
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments
	Method	Mixed Models Analysis
	Comments	Constrained longitudinal model adjusting for baseline stratification variables of diabetes status and blood pressure control.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -4.9 to 2.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Systolic Blood Pressure
Description	Continuous change in systolic blood pressure was measured as the primary outcome. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the18- month study visits.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

37 out of the 192 participants in the Titration Intervention group and 33 out of the 193 in the LPN control group had missing blood pressure measurement at 18 months due to not completing the assessment.

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	155	160
Mean (Standard Deviation) [mmHg]	136.1 (17.6)	138.0 (18.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Titration Intervention, LPN Control
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	Mixed Models Analysis
	Comments	Constrained longitudinal model adjusting for baseline stratification variables of diabetes status and blood pressure control.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -5.6 to 2.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Hypertension Control
Description	The investigators examined the difference in the degree of systolic BP control over the 18 months of the study between the intervention and control arms. Control was defined as SBP < 130mmHg for hypertensive patients with diabetes and < 140mmHg for patients without diabetes. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the baseline study visit.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Mean systolic blood pressure in control (units: participants)

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	192	193
Count of Participants [Participants]	47 24.5%	43 22.3%

6. Secondary Outcome

Title	Number of Participants With Hypertension Control
Description	The investigators examined the difference in the degree of systolic BP control over the 18 months of the study between the intervention and control arms. Control was defined as SBP < 130mmHg for hypertensive patients with diabetes and < 140mmHg for patients without diabetes. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the 6-month study visit.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

30 out of the 192 participants in the Titration Intervention group and 22 out of the 193 in the LPN control group had missing blood pressure measurement at 6 months due to not completing the assessment. One additional participant in the LPN control had missing blood pressure measurement at 6 months due to not being able to get a reading.

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	162	171
Count of Participants [Participants]	66 34.4%	63 32.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Titration Intervention, LPN Control
	Comments	Comparison at 6 months
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	Generalized Estimating Equation
	Comments	Generalized Estimating Equation with a Logit Link. Adjusted for baseline stratification variables of diabetes status.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; 0.7 to 1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Number of Participants With Hypertension Control
Description	The investigators examined the difference in the degree of systolic BP control over the 18 months of the study between the intervention and control arms. Control was defined as SBP < 130mmHg for hypertensive patients with diabetes and < 140mmHg for patients without diabetes. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the 12-study visit.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

53 out of the 192 participants in the Titration Intervention group and 34 out of the 193 in the LPN control group had missing blood pressure measurement at 12 months due to not completing the assessment.

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	139	159
Count of Participants [Participants]	58 30.2%	67 34.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Titration Intervention, LPN Control
	Comments	Comparison at 12 months
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments
	Method	Generalized Estimating Equation
	Comments	Generalized Estimating Equation with a Logit Link. Adjusted for baseline stratification variables of diabetes status.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; 0.5 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Number of Participants With Hypertension Control
Description	The investigators examined the difference in the degree of systolic BP control over the 18 months of the study between the intervention and control arms. Control was defined as SBP < 130mmHg for hypertensive patients with diabetes and < 140mmHg for patients without diabetes. Mean systolic blood pressure was calculated by the average of 3 blood pressure measurements collected at the18- month study visit.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

37 out of the 192 participants in the Titration Intervention group and 33 out of the 193 in the LPN control group had missing blood pressure measurement at 18 months due to not completing the assessment.

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	155	160
Count of Participants [Participants]	84 43.8%	69 35.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Titration Intervention, LPN Control
	Comments	Comparison at 18 months.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Generalized Estimating Equation
	Comments	Generalized Estimating Equation with a Logit Link. Adjusted for baseline stratification variables of diabetes status.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; 0.9 to 2.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Cost Effectiveness
Description	One of our secondary research questions was: "If the intervention results in greater reduction in SBP than the control group, is it cost effective?" Intervention results did not show statistically significant differences between arms, therefore cost effectiveness analysis was not appropriate. While cost effectiveness was not analyzed because it was a null trial, the investigators would have used resource utilization and cost data from VA data sets to measure VA outpatient and inpatient utilization and costs by arms over 18 months. The investigators would have examined hypertension-related outpatient pharmacy prescription counts and costs in order to compare them to total outpatient pharmacy costs and the investigators would have examined inpatient utilization and costs.
Time Frame	Over 18 months of study intervention

Outcome Measure Data

Analysis Population Description

Intervention results did not show statistically significant differences between arms, therefore cost effectiveness analysis is not appropriate.

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	0	0

10. Secondary Outcome

Title	Number of Participants Who Did Not Achieve Medication Adherence
Description	The investigators assessed adherence using patient self-report on a modified Morisky scale using 4 items: Do you ever forget to take your blood pressure medicine? Are you careless at times about taking your blood pressure medicine? When you feel better do you sometimes stop taking you blood pressure medicine? Sometimes if you feel worse when you take your blood pressure medicine, do you stop taking it? The scale is a Yes(0) or No (1) answer. A response of YES to any one of the 4 items indicated non-adherence, and responses of all no indicated adherence. The numbers in the descriptive tables reflect number non-adherent.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

The numbers in the descriptive tables reflect #non-adherent.

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	192	193
Count of Participants [Participants]	82 42.7%	82 42.5%

11. Secondary Outcome

Title	Number of Participants Who Did Not Achieve Medication Adherence
Description	The investigators assessed adherence using patient self-report on a modified Morisky scale using 4 items: Do you ever forget to take your blood pressure medicine? Are you careless at times about taking your blood pressure medicine? When you feel better do you sometimes stop taking you blood pressure medicine? Sometimes if you feel worse when you take your blood pressure medicine, do you stop taking it? The scale is a Yes(0) or No (1) answer. A response of YES to any one of the 4 items indicated non-adherence, and responses of all no indicated adherence. The numbers in the descriptive tables reflect number non-adherent.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

30 out of the 192 participants in the Titration Intervention group and 21 out of the 193 in the LPN control group had missing medication adherence at 6 months due to not completing the assessment. The numbers in the descriptive tables reflect #non-adherent.

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	162	172
Count of Participants [Participants]	62 32.3%	69 35.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Titration Intervention, LPN Control
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Generalized Estimating Equation
	Comments	Generalized Estimating Equation with a Logit Link. Adjusted for baseline stratification variable of diabetes status and diabetes control.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; 0.7 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Number of Participants Who Did Not Achieve Medication Adherence
Description	The investigators assessed adherence using patient self-report on a modified Morisky scale using 4 items: Do you ever forget to take your blood pressure medicine? Are you careless at times about taking your blood pressure medicine? When you feel better do you sometimes stop taking you blood pressure medicine? Sometimes if you feel worse when you take your blood pressure medicine, do you stop taking it? The scale is a Yes(0) or No (1) answer. A response of YES to any one of the 4 items indicated non-adherence, and responses of all no indicated adherence. The numbers in the descriptive tables reflect number non-adherent.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

53 out of the 192 participants in the Titration Intervention group and 34 out of the 193 in the LPN control group had missing medication adherence at 12 months due to not completing the assessment. The numbers in the descriptive tables reflect #non-adherent.

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	139	159
Count of Participants [Participants]	61 31.8%	59 30.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Titration Intervention, LPN Control
	Comments	Comparison at 12 months
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Generalized Estimating Equation
	Comments	Generalized Estimating Equation with a Logit Link.Adjusted for baseline stratification variable of diabetes status and blood pressure control.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; 0.9 to 2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Number of Participants Who Did Not Achieve Medication Adherence
Description	The investigators assessed adherence using patient self-report on a modified Morisky scale using 4 items: Do you ever forget to take your blood pressure medicine? Are you careless at times about taking your blood pressure medicine? When you feel better do you sometimes stop taking you blood pressure medicine? Sometimes if you feel worse when you take your blood pressure medicine, do you stop taking it? The scale is a Yes(0) or No (1) answer. A response of YES to any one of the 4 items indicated non-adherence, and responses of all no indicated adherence. The numbers in the descriptive tables reflect number non-adherent.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

37 out of the 192 participants in the Titration Intervention group and 33 out of the 193 in the LPN control group had missing medication adherence at 18 months due to not completing the assessment. The numbers in the descriptive tables reflect #non-adherent.

Arm/Group Title	Titration Intervention	LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.	A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
Measure Participants	155	160
Count of Participants [Participants]	73 38%	68 35.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Titration Intervention, LPN Control
	Comments	Comparison at 18 months
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Generalized Estimating Equation
	Comments	Generalized Estimating Equation with a Logit Link. Adjusted for baseline stratification variables of diabetes status and blood pressure control.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 0.8 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	18 months
Adverse Event Reporting Description	It is expected that these patients will have a variety of episodes related to cardiovascular and related diseases such as diabetes, age, smoking and drinking. These may include, but are not limited to, heart attack, stroke, and complications of diabetes among those patients with the disease, the diagnosis of cancer and dementia, development of disease of the lung or liver.
Arm/Group Title	Titration Intervention		LPN Control
Arm/Group Description	The intervention arm includes three levels of resource intensity targeted to improve patients' systolic blood pressure (SBP) [top number of blood pressure measurement]. Medium/level 1 resource intensity: a registered nurse (RN) will provide monthly tailored behavioral support telephone calls + home BP monitoring. High/level 2 resource intensity: a pharmacist will provide monthly tailored behavioral support telephone calls + home BP monitoring + pharmacist-directed medication management. Booster (low) resource intensity: a licensed practical nurse (LPN) will provide non-tailored behavioral support telephone calls every two months to patients whose SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.		A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months (identical to booster (low) resource intensity component of the titrated intervention). The control arm will utilize the same procedures as the booster level for intervention patients for whom SBP comes under control. Booster/ low resource: A LPN will provide behavioral support telephone calls that do not include goal setting and directed problem solving every two months.
All Cause Mortality
	Titration Intervention		LPN Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/192 (1.6%)		2/193 (1%)
Serious Adverse Events
	Titration Intervention		LPN Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/192 (20.8%)		9/193 (4.7%)
Blood and lymphatic system disorders
Hospitalization Other	0/192 (0%)	0	1/193 (0.5%)	1
Cardiac disorders
ER Visit	3/192 (1.6%)	4	0/193 (0%)	0
Heart Attack	3/192 (1.6%)	4	0/193 (0%)	0
Hospitalization Other	6/192 (3.1%)	7	3/193 (1.6%)	3
Other	1/192 (0.5%)	1	1/193 (0.5%)	1
Endocrine disorders
ER Visit	1/192 (0.5%)	1	0/193 (0%)	0
Gastrointestinal disorders
Hospitalization Other	1/192 (0.5%)	1	1/193 (0.5%)	1
General disorders
Hospitalization Other	1/192 (0.5%)	1	0/193 (0%)	0
Hepatobiliary disorders
Other	1/192 (0.5%)	1	0/193 (0%)	0
Infections and infestations
ER Visit	1/192 (0.5%)	1	1/193 (0.5%)	1
Hospitalization Other	1/192 (0.5%)	1	1/193 (0.5%)	1
Injury, poisoning and procedural complications
Hospitalization Other	2/192 (1%)	2	0/193 (0%)	0
Musculoskeletal and connective tissue disorders
Hospitalization Other	2/192 (1%)	2	0/193 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hospitalization Other	2/192 (1%)	2	0/193 (0%)	0
Other	2/192 (1%)	2	0/193 (0%)	0
Renal and urinary disorders
ER Visit	0/192 (0%)	0	1/193 (0.5%)	1
Hospitalization Other	2/192 (1%)	3	0/193 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hospitalization Other	2/192 (1%)	2	0/193 (0%)	0
Surgical and medical procedures
Hospitalization Other	7/192 (3.6%)	10	0/193 (0%)	0
Vascular disorders
Hospitalization Other	1/192 (0.5%)	1	0/193 (0%)	0
Other	1/192 (0.5%)	1	0/193 (0%)	0
Other (Not Including Serious) Adverse Events
	Titration Intervention		LPN Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	117/192 (60.9%)		112/193 (58%)
Cardiac disorders
ER Visit	13/192 (6.8%)	15	15/193 (7.8%)	25
Hospitalization Other	11/192 (5.7%)	11	11/193 (5.7%)	19
Gastrointestinal disorders
ER Visit	9/192 (4.7%)	9	6/193 (3.1%)	7
General disorders
ER Visit	20/192 (10.4%)	24	22/193 (11.4%)	31
Infections and infestations
ER Visit	17/192 (8.9%)	20	21/193 (10.9%)	31
Injury, poisoning and procedural complications
ER Visit	13/192 (6.8%)	14	2/193 (1%)	2
Musculoskeletal and connective tissue disorders
ER Visit	20/192 (10.4%)	31	26/193 (13.5%)	39
Respiratory, thoracic and mediastinal disorders
ER Visit	4/192 (2.1%)	4	9/193 (4.7%)	12
Surgical and medical procedures
Hospitalization Other	11/192 (5.7%)	12	11/193 (5.7%)	13

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.