Intima Versus Adventitia Drug Delivery to Elucidate Mecha... | NCT02807779

NCT02807779

ID	Type	Description	Link
1R01HL128816-01	U.S. NIH Grant/Contract		View source

Status Module

Sponsor/Collaborators Module

Name	Class
University of Washington	OTHER
National Heart, Lung, and Blood Institute (NHLBI)	NIH

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Dexamethasone	Experimental	Participants randomized to the Dexamethasone group will receive dexamethasone infusion to the adventitia of the artery following plain-old-balloon-angioplasty (POBA).	Drug: Dexamethasone infusion
Drug Coated Balloon	Active Comparator	Participants randomized to the Drug Coated Balloon (DCB) group will not receive dexamethasone infusion to the adventitia of the artery following (POBA). They will receive additional angioplasty with a paclitaxel coated balloon.	Device: Drug coated balloon
Plain Balloon Angioplasty	Active Comparator	Participants randomized to the Plain Balloon Angioplasty will receive balloon angioplasty (POBA) only. They will not receive a dexamethasone infusion to the adventitia or paclitaxel.	Device: Plain balloon angioplasty

Name	Type	Description	Arm Group Labels	Other Names
Dexamethasone infusion	Drug	Participants will receive dexamethasone infusion following plain balloon angioplasty	Dexamethasone

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Percent Wall Volume (PWV)	The change in percent wall volume (PWV) of the treated segment between the postoperative and 12 month time points as measured by MRI	From Post-Operative Day One to 12 Months

Secondary Outcomes

Measure	Description	Time Frame
Change in Wall Volume (WV) Without a Change in Total Vessel Volume (TVV)	The change in wall volume (WV) without change in total vessel volume (TVV) of the treated segment between the postoperative and 12 month time points as measured by MRI	From Post-Operative Day One to 12 Months
Change in Perioperative Inflammatory Profile (MCP-1)

Measure	Description	Time Frame
Extended Clinical Adverse Events Monitoring	Participant monitoring for clinical adverse events	From Post-Operative Day One to 36 Months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Screening:

Male or non-pregnant female ≥ 35 years of age
Atherosclerotic, infrainguinal PAD
Rutherford Clinical Category 2-6
Stenosis detected by radiology that in the clinician's opinion is the reason for the PAD symptoms
Patient is willing to provide informed consent and comply with the required follow up visits, testing schedule, and medication regimen
Estimated Glomerular Filtration Rate (eGFR) ≥ 30 and/or threshold established by the local Institutional Review Board or Committee of Human Research

Procedural Criteria:

De novo atherosclerotic lesion qualifying for angioplasty
A patent artery proximal to the index lesion. Concomitant inflow procedures, including open femoral artery endarterectomy and/or stenting of the iliac arteries, are permissible.
>50% diameter stenosis of the superficial femoral artery and/or popliteal artery (between the profunda and tibioperoneal trunk)
Reference vessel diameter ≥3 mm and ≤ 8mm
Successful wire crossing of lesion
Successful angioplasty of the index lesion or part of the index lesion, defined as ≤30% residual lumen stenosis compared with adjacent non-diseased lumen diameter, without flow-limiting dissection

Exclusion Criteria:

Screening Criteria:

Any contraindication to receiving an MRI
Pregnant, nursing, or planning on becoming pregnant in < 2yrs
Life expectancy of < 1 yr
History of solid organ transplantation
Patient actively participating in another investigational device or drug study
History of hemorrhagic stroke within 3 months of index procedure
Previous or planned surgical or interventional procedure within 30 days of index procedure
Chronic renal insufficiency with eGFR < 30
Prior bypass surgery, stenting, atherectomy or angioplasty of the index lesion
Inability to take required study medications
Contra-indication or known hypersensitivity to dexamethasone sodium phosphate, contrast media, gadolinium, aspirin or Plavix
Systemic fungal infection
Acute limb ischemia
Prior participation of the index limb in the current study (contralateral treatment is allowed)
Patient is being treated with long-term steroids (not including treatment of a bronchial condition with inhaled steroids)

Procedural Criteria:

Index lesions extending into the tibial trifurcation or above the profunda. Note: the outflow tibial artery can be treated concomitantly. Similarly, the common femoral artery can be treated concomitantly, either with open endarterectomy and patch angioplasty or with endovascular methods. However, the index lesion cannot be contiguous with either the common femoral artery or the tibial trifurcation.
Circumferential calcification at index lesion, which in the judgment of the investigator would prevent penetration of the Micro-Infusion catheter needle through the vessel wall
Inadequate distal outflow defined as no patent tibial arteries (>50% stenosis). The outflow vessel can be established at the time of primary treatment
Use of adjunctive therapies other than angioplasty. Chocolate balloons and/or scoring balloons are allowed, if used below reference diameter.

Contacts/Locations Module

Name	Affiliation	Role
Warren Gasper, MD	San Francisco VA Medical Center	Principal Investigator
David Saloner, PhD	San Francisco VA Medical Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
San Francisco VA Medical Center		San Francisco	California	94121	United States
University of Washington

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Dexamethasone	Participants received dexamethasone infusion to the adventitia of the treated artery (1.6mg per cm of artery) following plain-old-balloon-angioplasty (POBA). Dexamethasone infusion: Dexamethasone infusion to the artery adventitia (1.6mg per cm of artery) following plain balloon angioplasty
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Oct 10, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

microinfusion catheter

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Dexamethasone	Participants received dexamethasone infusion to the adventitia of the treated artery (1.6mg per cm of artery) following plain-old-balloon-angioplasty (POBA). Dexamethasone infusion: Dexamethasone infusion to the artery adventitia (1.6mg per cm of artery) following plain balloon angioplasty
BG001	Drug-Coated Balloon	Participants received additional angioplasty with a paclitaxel drug-coated balloon (DCB) of the treated artery following plain-old-balloon-angioplasty (POBA). Drug-coated balloon: Angioplasty with a paclitaxel drug-coated balloon following plain balloon angioplasty
BG002	Plain Balloon Angioplasty	Participants received plain-old-ballon-angioplasty (POBA) only. Plain balloon angioplasty: Participants will receive plain balloon angioplasty only
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00010 BG0019 BG0021 BG00320

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00067± 7.5 BG00167.6± 9.9 BG00276± 0 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000 BG0011 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Hypertension

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00010 BG0018 BG002

Hyperlipidemia

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG0009 BG0016 BG002

Diabetes mellitus

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG0005 BG0013 BG002

Coronary artery disease

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG0006 BG0012 BG002

Rutherford category

Rutherford category 1-3 refer to intermittent claudication, less severe presentations of peripheral artery disease Rutherford category 4 refers to ischemic rest pain, a severe presentation of peripheral artery disease Rutherford category 5 refers to ischemic wounds, a severe presentation of peripheral artery disease

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Rutherford category 1	BG0000 BG001

White blood cell count

Mean

Standard Deviation

10^9 cells/L

Title

Denominators

Categories

Title	Measurements
	BG0008.6± 1.8 BG0017.9± 2.2 BG002

Hemoglobin

Mean

Standard Deviation

g/dL

Title

Denominators

Categories

Title	Measurements
	BG00012.3± 1.6 BG00112.9± 1.1 BG002

Hematocrit

Mean

Standard Deviation

percentage of hematocrit

Title

Denominators

Categories

Title	Measurements
	BG00037.5± 4.8 BG00138.8± 3.2 BG002

Platelet count

Mean

Standard Deviation

10^9 platelets/L

Title

Denominators

Categories

Title	Measurements
	BG000225.1± 62.3 BG001244.5± 62.9 BG002

C-Reactive Protein (CRP)

Median

Inter-Quartile Range

mg/L

Title

Denominators

Categories

Title	Measurements
	BG0003.5(1.6 to 12.3) BG0012.0(1.0 to 3.6) BG002

Monocyte Chemotactic Protein 1 (MCP-1)

Mean

Standard Deviation

pg/mL

Title

Denominators

Categories

Title	Measurements
	BG00072.6± 21.5 BG00177.1± 19.6 BG002

Interleukin 1 Beta (IL-1beta)

Median

Inter-Quartile Range

pg/mL

Title

Denominators

Categories

Title	Measurements
	BG0000.19(0.11 to 0.91) BG0010.17(0.10 to 0.24) BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in Percent Wall Volume (PWV)

The change in percent wall volume (PWV) of the treated segment between the postoperative and 12 month time points as measured by MRI

No data was collected for the Plain Balloon Angioplasty group

Posted

Mean

Standard Deviation

Percent Wall Volume

From Post-Operative Day One to 12 Months

ID	Title	Description
OG000	Dexamethasone	Participants received dexamethasone infusion to the adventitia of the treated artery (1.6mg per cm of artery) following plain-old-balloon-angioplasty (POBA). Dexamethasone infusion: Dexamethasone infusion to the artery adventitia (1.6mg per cm of artery) following plain balloon angioplasty
OG001	Drug-Coated Balloon	Participants received additional angioplasty with a paclitaxel drug-coated balloon (DCB) of the treated artery following plain-old-balloon-angioplasty (POBA). Drug-coated balloon: Angioplasty with a paclitaxel drug-coated balloon following plain balloon angioplasty
OG002	Plain Balloon Angioplasty	Participants received plain-old-ballon-angioplasty (POBA) only. Plain balloon angioplasty: Participants will receive plain balloon angioplasty only

Units	Counts
Participants	OG0005 OG0014 OG0020

Title

Denominators

Categories

Title	Measurements
	OG00012.3± 11.6 OG0013.9± 4.3

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Power calculations were performed based on an expected reproducibility variance of 8% and an effect size of 7% was assumed based on data from pilot studies. It was estimated that 22 subjects/treatment assignment were needed to detect a 7% difference in PWV at a power level of 80%. Assigning a 20% attrition rate due to loss to follow up or index lesion revascularization, the goal enrollment was 27 subjects per arm. No subjects in the plain balloon angioplasty group had MRI data for analysis.	t-test, 2 sided		0.22	Threshold for statistical significance was p=0.05.													Superiority

Secondary

Change in Wall Volume (WV) Without a Change in Total Vessel Volume (TVV)

The change in wall volume (WV) without change in total vessel volume (TVV) of the treated segment between the postoperative and 12 month time points as measured by MRI

No data was collected for the Plain Balloon Angioplasty group

Posted

Mean

Standard Deviation

mm*3

From Post-Operative Day One to 12 Months

ID	Title	Description
OG000	Dexamethasone	Participants received dexamethasone infusion to the adventitia of the treated artery (1.6mg per cm of artery) following plain-old-balloon-angioplasty (POBA). Dexamethasone infusion: Dexamethasone infusion to the artery adventitia (1.6mg per cm of artery) following plain balloon angioplasty
OG001	Drug-Coated Balloon	Participants received additional angioplasty with a paclitaxel drug-coated balloon (DCB) of the treated artery following plain-old-balloon-angioplasty (POBA). Drug-coated balloon: Angioplasty with a paclitaxel drug-coated balloon following plain balloon angioplasty
OG002	Plain Balloon Angioplasty	Participants received plain-old-ballon-angioplasty (POBA) only. Plain balloon angioplasty: Participants will receive plain balloon angioplasty only

Secondary

Change in Perioperative Inflammatory Profile (MCP-1)

The serum concentration of monocyte chemoattractant protein-1 (MCP-1) between postprocedure day 1 and 12 months postprocedure. Reported as the area under the curve (AUC) of the MCP-1 concentration (postprocedure day 1, 1 month and 12 months)

No data was collected for the Plain Balloon Angioplasty group

Posted

Mean

Standard Deviation

pg*d/mL

From Post-Operative Day One to 12 Months

ID	Title	Description
OG000	Dexamethasone	Participants received dexamethasone infusion to the adventitia of the treated artery (1.6mg per cm of artery) following plain-old-balloon-angioplasty (POBA). Dexamethasone infusion: Dexamethasone infusion to the artery adventitia (1.6mg per cm of artery) following plain balloon angioplasty
OG001	Drug-Coated Balloon	Participants received additional angioplasty with a paclitaxel drug-coated balloon (DCB) of the treated artery following plain-old-balloon-angioplasty (POBA). Drug-coated balloon: Angioplasty with a paclitaxel drug-coated balloon following plain balloon angioplasty
OG002	Plain Balloon Angioplasty	Participants received plain-old-ballon-angioplasty (POBA) only. Plain balloon angioplasty: Participants will receive plain balloon angioplasty only

Secondary

Change in Perioperative Inflammatory Profile (CRP)

The serum concentration of C-reactive protein (CRP) between postprocedure day 1 and 12 months postprocedure. Reported as the area under the curve (AUC) of the CRP concentration (postprocedure day 1, 1 month and 12 months).

No data was collected for the Plain Balloon Angioplasty group

Posted

Mean

Standard Deviation

mg*d/L

From Post-Operative Day One to 12 Months

ID	Title	Description
OG000	Dexamethasone	Participants received dexamethasone infusion to the adventitia of the treated artery (1.6mg per cm of artery) following plain-old-balloon-angioplasty (POBA). Dexamethasone infusion: Dexamethasone infusion to the artery adventitia (1.6mg per cm of artery) following plain balloon angioplasty
OG001	Drug-Coated Balloon	Participants received additional angioplasty with a paclitaxel drug-coated balloon (DCB) of the treated artery following plain-old-balloon-angioplasty (POBA). Drug-coated balloon: Angioplasty with a paclitaxel drug-coated balloon following plain balloon angioplasty
OG002	Plain Balloon Angioplasty	Participants received plain-old-ballon-angioplasty (POBA) only. Plain balloon angioplasty: Participants will receive plain balloon angioplasty only

Secondary

Change in Perioperative Inflammatory Profile (IL-1beta)

The serum concentration of interleukin-1beta (IL-1beta) between postprocedure day 1 and 12 months postprocedure. Reported as the area under the curve (AUC) of the IL-1beta concentration (postprocedure day 1, 1 month and 12 months).

No subject had measurable serum IL-1beta at the 12month timepoint

Posted

From Post-Operative Day One to 12 Months

ID	Title	Description
OG000	Dexamethasone	Participants received dexamethasone infusion to the adventitia of the treated artery (1.6mg per cm of artery) following plain-old-balloon-angioplasty (POBA). Dexamethasone infusion: Dexamethasone infusion to the artery adventitia (1.6mg per cm of artery) following plain balloon angioplasty
OG001	Drug-Coated Balloon	Participants received additional angioplasty with a paclitaxel drug-coated balloon (DCB) of the treated artery following plain-old-balloon-angioplasty (POBA). Drug-coated balloon: Angioplasty with a paclitaxel drug-coated balloon following plain balloon angioplasty
OG002	Plain Balloon Angioplasty	Participants received plain-old-ballon-angioplasty (POBA) only. Plain balloon angioplasty: Participants will receive plain balloon angioplasty only

Secondary

Change in Transfer Constant (Ktrans)

The change in adventitial transfer constant (Ktrans) of the treated segment between the postoperative and 6 month time points as measured by dynamic contrast enhanced MRI

No data was collected for the Plain Balloon Angioplasty group

Posted

Mean

Standard Deviation

min^-1

From 1 Month to 6 Months

ID	Title	Description
OG000	Dexamethasone	Participants received dexamethasone infusion to the adventitia of the treated artery (1.6mg per cm of artery) following plain-old-balloon-angioplasty (POBA). Dexamethasone infusion: Dexamethasone infusion to the artery adventitia (1.6mg per cm of artery) following plain balloon angioplasty
OG001	Drug-Coated Balloon	Participants received additional angioplasty with a paclitaxel drug-coated balloon (DCB) of the treated artery following plain-old-balloon-angioplasty (POBA). Drug-coated balloon: Angioplasty with a paclitaxel drug-coated balloon following plain balloon angioplasty
OG002	Plain Balloon Angioplasty	Participants received plain-old-ballon-angioplasty (POBA) only. Plain balloon angioplasty: Participants will receive plain balloon angioplasty only

Secondary

Change in Lumen Volume (LV) Relative to Total Vessel Volume (TVV)

The change in lumen volume (LV) relative to total vessel volume (TVV) of the treated segment between the postoperative and 12 month time points as measured by MRI

No data was collected for the Plain Balloon Angioplasty group

Posted

Mean

Standard Deviation

mm*3

From Post-Operative Day One to 12 Months

ID	Title	Description
OG000	Dexamethasone	Participants received dexamethasone infusion to the adventitia of the treated artery (1.6mg per cm of artery) following plain-old-balloon-angioplasty (POBA). Dexamethasone infusion: Dexamethasone infusion to the artery adventitia (1.6mg per cm of artery) following plain balloon angioplasty
OG001	Drug-Coated Balloon	Participants received additional angioplasty with a paclitaxel drug-coated balloon (DCB) of the treated artery following plain-old-balloon-angioplasty (POBA). Drug-coated balloon: Angioplasty with a paclitaxel drug-coated balloon following plain balloon angioplasty
OG002	Plain Balloon Angioplasty	Participants received plain-old-ballon-angioplasty (POBA) only. Plain balloon angioplasty: Participants will receive plain balloon angioplasty only

Secondary

Percentage of Subjects With Clinically Significant Restenosis That Undergo Reintervention of Greater Than or Equal to 75% of the Treated Segment

Percentage of subjects with clinically significant restenosis that undergo reintervention of greater than or equal to 75% of the treated segment by the 12 month timepoint.

Posted

Count of Participants

Participants

From Post-Operative Day One to 12 Months

ID	Title	Description
OG000	Dexamethasone	Participants received dexamethasone infusion to the adventitia of the treated artery (1.6mg per cm of artery) following plain-old-balloon-angioplasty (POBA). Dexamethasone infusion: Dexamethasone infusion to the artery adventitia (1.6mg per cm of artery) following plain balloon angioplasty
OG001	Drug-Coated Balloon	Participants received additional angioplasty with a paclitaxel drug-coated balloon (DCB) of the treated artery following plain-old-balloon-angioplasty (POBA). Drug-coated balloon: Angioplasty with a paclitaxel drug-coated balloon following plain balloon angioplasty
OG002	Plain Balloon Angioplasty	Participants received plain-old-ballon-angioplasty (POBA) only. Plain balloon angioplasty: Participants will receive plain balloon angioplasty only

Other Pre-specified

Extended Clinical Adverse Events Monitoring

Participant monitoring for clinical adverse events

Not Posted

From Post-Operative Day One to 36 Months

Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dexamethasone	Participants received dexamethasone infusion to the adventitia of the treated artery (1.6mg per cm of artery) following plain-old-balloon-angioplasty (POBA). Dexamethasone infusion: Dexamethasone infusion to the artery adventitia (1.6mg per cm of artery) following plain balloon angioplasty	1	10	7	10	1	10
EG001	Drug-Coated Balloon	Participants received additional angioplasty with a paclitaxel drug-coated balloon (DCB) of the treated artery following plain-old-balloon-angioplasty (POBA). Drug-coated balloon: Angioplasty with a paclitaxel drug-coated balloon following plain balloon angioplasty	1	9	7	9	1	9
EG002	Plain Balloon Angioplasty	Participants received plain-old-ballon-angioplasty (POBA) only. Plain balloon angioplasty: Participants will receive plain balloon angioplasty only	0	1	1	1	0	1

Serious Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Death	Cardiac disorders	Systematic Assessment		EG0001 events1 affected10 at risk EG0011 events1 affected9 at risk EG0020 events0 affected1 at risk
Reintervention requiring hospitalization	Vascular disorders	Systematic Assessment	Repeat procedure on the arteries of the treated (index) or non-treated (non-index) leg requiring hospitalization	EG00010 events5 affected10 at risk EG0017 events6 affected9 at risk EG0022 events1 affected1 at risk
COVID pneumonia requiring hospitalization	Respiratory, thoracic and mediastinal disorders	Systematic Assessment		EG0001 events1 affected10 at risk EG0010 affected9 at risk EG0020 affected1 at risk
Acute heart failure requiring admission	Cardiac disorders	Systematic Assessment		EG0001 events1 affected10 at risk EG0010 affected9 at risk EG0020 affected1 at risk
Arterial access site pseudoaneurysm requiring operation	Vascular disorders	Systematic Assessment		EG0000 affected10 at risk EG0010 affected9 at risk EG0021 events1 affected1 at risk
Unstable angina requiring coronary revascularization	Cardiac disorders	Systematic Assessment		EG0001 events1 affected10 at risk EG0010 affected9 at risk EG0020 affected1 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Pacemaker placement	Cardiac disorders		Systematic Assessment		EG0001 events1 affected10 at risk EG0010 affected9 at risk EG0020 affected1 at risk
Urinary tract infection	Renal and urinary disorders		Systematic Assessment	Urinary tract infection leading to ER visit	EG0000 affected10 at risk EG0011 affected9 at risk EG0020 affected1 at risk

ID	Term
D058729	Peripheral Arterial Disease
D014652	Vascular Diseases
D000089802	Chronic Limb-Threatening Ischemia
D016491	Peripheral Vascular Diseases
D050197	Atherosclerosis
D007383	Intermittent Claudication

Ancestor Terms

ID	Term
D001161	Arteriosclerosis
D001157	Arterial Occlusive Diseases
D002318	Cardiovascular Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D007511	Ischemia
D012816	Signs and Symptoms

BG0032.1(.96 to 6.4)

BG0030.19(0.11 to 0.24)