Protocol 201

Design, Procedures, Findings

and Issues from the Largest

NIH-funded Dysphagia Clinical

Trial

Entitled:

Randomized Study of Two Interventions for

Liquid Aspiration:

Short- and Long-term Effects

(aka: “Protocol 201”)

Commercial Relationships: Novartis Food Service Division™, E-Z-EM, Inc.™

Supported by Grant #DC03206 to ASHA from DHHS/NIH/NIDCD

When, Why and How?

1995

NIH Request for Applications

for Clinical Trials

Jeri Logemann, ASHA president

Herb Baum, Director of Research ASHA

Fred Spahr, Executive Director of ASHA

Overview of Study Design

Jeri A. Logemann, PhD, CCC-SLP, BRS-S

Principal Investigator, CSDRG

Northwestern University

Evanston, Illinois

Methods-Part I

All patients received all 3 interventions in

a randomly assigned order during

videofluoroscopic swallow study and

observed for aspiration.

Interventions:

Chin-down

Nectar Viscosity

Honey viscosity

Randomly Assigned Order

Methods-Part II

Patients in Part II of the study were

those who either succeeded in

eliminating aspiration with all

interventions or failed and continued to

aspirate despite all interventions.

Methods-Part II

Patients in Part II were randomized

between Chin-down posturing and

Thickened Liquids.

Patients randomized to Thickened

Liquids were further randomized

Patients in Part II were randomized to

one of the three interventions and

followed for 3 months for pneumonia.

Aspiration Rates by Diagnosis

None of the interventions            All of the interventions

Parkinson’s disease                      32%                                       39%

Dementia 25%                                                     55%

Parkinson’s with dementia  26%                          50%

Overall                                   25%                            49%

Summary

Higher proportion of dementia pts

aspirated on all interventions

Aspiration frequency: Chin down,

nectar, then honey

Older patients had a lower aspiration

rate (chin-down or honey)

Aspiration on honey higher when

administered last

More severe dementia associated

with more frequent aspiration

Part II: Long-term Effects

Design and Methods

Population

• Parkinson’s disease and/or

dementia

• Age 50-95

• No confounding medical issues

Population

• Aspirate on thin liquids

• Aspirate on all three

interventions or none

Primary Outcome

Definite Pneumonia

• Evidence of pneumonia on chest

x-ray

• OR

• Three or more of:

• Sustained febrile illness >100°F

• Presence rales or rhonchi

• Positive Sputum grams stain

• Positive Sputum culture

Part II: Design

Chin-down Posturing N=290

Total Sample N=580

Honey Viscosity N=145

Thickened Liquids N=290

Nectar Viscosity N=145

Enrollment

• Began: 06/09/1998

• Terminated: 09/16/2005

• 47 acute care hospitals

• 79 sub-acute residential facilities

• Enrolled 515 study participants

Enrollment

515 Enrolled

413 Completed follow-up no death or pneumonia

39 Died without pneumonia

52 Pneumonia (21 Died)

11 Incomplete follow  up (1 Died)

Part II: Design

Chin-down Posturing N=259

Total Sample N=515

Honey Viscosity N=133

Thickened Liquids N=256

Nectar  Viscosity N=123

Analytic Methods

• Kaplan-Meier estimates of

pneumonia incidence

• Cox proportional hazards model to

estimate treatment effect after

adjustment for risk factors

• Deaths and losses to follow-up

prior to pneumonia censored

Results and Clinical

Applications

JoAnne Robbins, PhD, CCC-SLP, BRS-S

Study Chair

University of Wisconsin

William S. Middleton Memorial VA Hospital

Madison, WI

Protocol 201 Long Term Findings

Demographics (N=515)

70% male

59% > 80 years

16% minorities

Diagnostic Groups

50% dementia

30% Parkinson’s disease

20% Parkinson’s + dementia

Approximately 2/3 qualified by aspiration on ALL 3 interventions

Protocol 201 Estimates of Pneumonia

Incidence by Intervention

Kaplan-Meier Probability of

Pneumonia Incidence

Chin down Thickened liquids p=0.53

Protocol 201 Estimates of Pneumonia

Incidence by Intervention

Honey vs. Nectar

Kaplan-Meier Probability of

Pneumonia Incidence

Nectar-thickened Honey-thickened p=0.08*

*More than two fold increase in pneumonia incidence in

honey thickened intervention compared to nectar thick

Pneumonia:

Long Term Findings:

Subjects with dementia with or without PD had

significantly higher incidence of pneumonia than

PD only (15% vs. 5%, p<0.05)

Subjects who aspirated on all 3 interventions had

a significantly higher incidence of pneumonia

than subjects who aspirated on none of the

interventions (14% vs. 6%, p<0.05)

Parkinson’s Disease Group (no dementia)

10%* vs. 0%, p=0.052

*All had severe PD by Hoehn and Yahr rating

Patients randomized to honey thick had

greater pneumonia rates than those

randomized to nectar thick

Subjects Randomized to

Thickened Liquids (N=256)

Aspirated on all interventions

• More pneumonias than aspirated on none (p=.05)

Randomized to honey thick

• More pneumonias than nectar (p=.06 adjusted)

Part II Pneumonia relative to Part I Performance

Aspiration group x treatment p=0.09

Secondary Outcomes

• Prescribed antibiotics

• N=303 (151 chin down, 152 thickened liquids)

• Chin down: 12% on antibiotics

• Thickened liquids: 19% on antibiotics • p=.09

• Of those on thickened liquids:

• Nectar thickened 14%

• Honey thickened 25%

• p=.07

Major Findings

Long term results show that despite

differential effect of interventions on

immediate elimination of aspiration

in videofluoroscopic suite

(Part I findings)…

…the 3-month incidence of pneumonia

was similar for chin down posture

compared to thickened liquids

Adverse Events

Hospitalization

Dehydration

Hospitalization

Balanced across interventions

Median length of hospital stay due to pneumonia:

# Days

Honey                                     19

Chin                                    6

 Nectar                          5

Dehydration

No difference in measured parameters

Subset: n=16

Serum osmolality

Sodium

BUN (mg/dL)

Serum creatine (mg/dL)

Defined by primary physician

Was more frequent with thickened liquid

(6% vs. 2%, p<0.05)

Overall, no statistically significant difference in pneumonia incidence  between chin down and thickened liquid conditions

Long Term Findings:

Current Clinical Notion

“The thicker the liquid,

the safer the swallow”

*Not true in patients who aspirate thick liquids –

worse health outcomes

Subjects who succeeded with one or two interventions, were

not followed for health outcomes