## Protocol Section
### Identification Module
**NCT ID:** NCT01048879

**Brief Title:** Pharmacokinetics of Tamiflu® (Oseltamivir) in Patients Receiving Extracorporeal Membrane Oxygenation (ECMO)and or Continuous Venovenous Hemodialysis (CVVHD)

**Official Title:** Pharmacokinetics of Tamiflu® (Oseltamivir) in Patients Receiving CVVHD and/or ECMO

#### Organization Study ID Info
**ID:** HUM00033929
#### Organization
**Class:** OTHER
**Full Name:** University of Michigan
### Status Module
#### Completion Date
**Date:** 2010-01

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2012-08-21

**Type:** ESTIMATED

**Last Update Submit Date:** 2012-07-17

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2010-01

**Type:** ACTUAL

#### Results First Post Date
**Date:** 2012-08-21

**Type:** ESTIMATED

**Results First Submit Date:** 2012-06-13

**Results First Submit QC Date:** 2012-07-17

#### Start Date
**Date:** 2009-10

**Status Verified Date:** 2012-07

#### Study First Post Date
**Date:** 2010-01-14
**Type:** ESTIMATED
**Study First Submit Date:** 2010-01-13
**Study First Submit QC Date:** 2010-01-13
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Roche Pharma AG

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Michigan

#### Responsible Party

**Investigator Affiliation:** University of Michigan

**Investigator Full Name:** Bruce A. Mueller

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Critically ill patients with flu may receive a drug called oseltamivir. They may also receive medical therapies to support their lung function (extracorporeal membrane oxygenation; ECMO) and kidney function (continuous venovenous hemodialysis; CVVHD). CVVHD and ECMO may remove some oseltamivir from the bloodstream. The purpose of this study is to determine how much oseltamivir gets removed by CVVHD or ECMO in critically ill patients.

### Conditions Module

**Conditions:**

- Critically Ill Renal Failure Requiring CVVHD and Oseltamivir

- Critically Ill Requiring ECMO and Oseltamivir

**Keywords:**

- oseltamivir

- influenza

- continuous renal replacement therapy

- extracorporeal membrane oxygenation

- pharmacokinetics

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 15

**Type:** ACTUAL

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Patients receiving oseltamivir and Extracorporeal Membrane Oxygenation (ECMO) therapy (patients were already receiving oseltamivir and ECMO due to an illness)- Procedure/Surgery: pharmacokinetic blood sampling

**Intervention Names:**

- Procedure: pharmacokinetic blood sampling

**Label:** ECMO alone

**Type:** OTHER

#### Arm Group 2

**Description:** Patients receiving Continuous Venovenous Hemodialysis(CVVHD) and oseltamivir (Patients were already receiving oseltamivir and CVVHD as a result of an illness).

Procedure/Surgery: pharmacokinetic blood and dialysate sampling

**Intervention Names:**

- Procedure: pharmacokinetic blood and dialysate sampling

**Label:** CVVHD Alone

**Type:** OTHER

#### Arm Group 3

**Description:** Patient receiving oseltamivir and ECMO and CVVHD (patients were already receiving oseltamivir, ECMO, and CVVHD as part of an illness).

Procedure/Surgery: pharmacokinetic blood and dialysate sampling

**Intervention Names:**

- Procedure: pharmacokinetic blood and dialysate sampling

**Label:** CVVHD + ECMO

**Type:** OTHER

### Interventions

#### Intervention 1

**Arm Group Labels:**

- ECMO alone

**Description:** blood samples collected to assess oseltamivir concentrations

**Name:** pharmacokinetic blood sampling

**Other Names:**

- Tamiflu

**Type:** PROCEDURE

#### Intervention 2

**Arm Group Labels:**

- CVVHD + ECMO

- CVVHD Alone

**Description:** blood and dialysate samples collected and assayed for oseltamivir concentrations

**Name:** pharmacokinetic blood and dialysate sampling

**Other Names:**

- Tamiflu

**Type:** PROCEDURE

### Outcomes Module

#### Primary Outcomes

**Description:** Oseltamivir Carboxylate Transmembrane Clearance by Continuous Venovenous Hemodialysis (Reported in mL/min).

**Measure:** Continuous Venovenous Hemodialysis (CVVHD)Oseltamivir Carboxylate Transmembrane Clearance

**Time Frame:** 12 hours

**Description:** Mean percent change in oseltamivir carboxylate concentration pre- and post-oxygenator.

**Measure:** Oseltamivir Carboxylate Removal by ECMO

**Time Frame:** 12 hours

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* receiving Continuous Venovenous Hemodialysis (CVVHD) or Extracorporeal Membrane Oxygenation (ECMO)
* require oseltamivir treatment
* informed consent granted

Exclusion Criteria:

* pregnant
* unable to complete 12 hours of CVVHD or ECMO
* \<6 kg body weight
* allergy to oseltamivir

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Ann Arbor

**Country:** United States

**Facility:** University of Michigan Hospital

**State:** Michigan

**Zip:** 48109

#### Overall Officials

**Official 1:**

**Affiliation:** University of Michigan

**Name:** Bruce A Mueller, Pharm.D.

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** Eyler RF, Heung M, Pleva M, Sowinski KM, Park PK, Napolitano LM, Mueller BA. Pharmacokinetics of oseltamivir and oseltamivir carboxylate in critically ill patients receiving continuous venovenous hemodialysis and/or extracorporeal membrane oxygenation. Pharmacotherapy. 2012 Dec;32(12):1061-9. doi: 10.1002/phar.1151.

**PMID:** 23208833

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC01

- Name: Infections

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

### Condition Browse Module - Browse Leaves

- ID: M19010

- Name: Critical Illness

- Relevance: HIGH

- As Found: Critically Ill

- ID: M10295

- Name: Influenza, Human

- Relevance: LOW

- As Found: Unknown

- ID: M26718

- Name: Renal Insufficiency

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000016638

- Term: Critical Illness

### Intervention Browse Module - Ancestors

- ID: D000019999

- Term: Pharmaceutical Solutions

- ID: D000000998

- Term: Antiviral Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: PhSol

- Name: Pharmaceutical Solutions

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infe

- Name: Anti-Infective Agents

### Intervention Browse Module - Browse Leaves

- ID: M18008

- Name: Dialysis Solutions

- Relevance: HIGH

- As Found: Immunosuppression

- ID: M27146

- Name: Oseltamivir

- Relevance: HIGH

- As Found: Repetitions of

- ID: M21860

- Name: Pharmaceutical Solutions

- Relevance: LOW

- As Found: Unknown

- ID: M4314

- Name: Antiviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000053139

- Term: Oseltamivir

- ID: D000015314

- Term: Dialysis Solutions

### Misc Info Module

- Version Holder: 2024-05-24

## Results Section

### Adverse Events Module

#### Event Groups

**Group ID:** EG000

**Title:** ECMO Alone

**Description:** Patients receiving oseltamivir and Extracorporeal Membrane Oxygenation (ECMO) therapy

**ID:** EG000

**Other Num at Risk:** 1

**Serious Number At Risk:** 1

**Title:** ECMO Alone

**Group ID:** EG001

**Title:** CVVHD Alone

**Description:** Patients receiving Continuous Venovenous Hemodialysis(CVVHD) and oseltamivir

**ID:** EG001

**Other Num at Risk:** 9

**Serious Number At Risk:** 9

**Title:** CVVHD Alone

**Group ID:** EG002

**Title:** CVVHD + ECMO

**Description:** Patient receiving oseltamivir and ECMO and CVVHD

**ID:** EG002

**Other Num at Risk:** 5

**Serious Number At Risk:** 5

**Title:** CVVHD + ECMO

**Frequency Threshold:** 5

## Results Section - Baseline Characteristics Module

### Denomination Counts

**Group ID:** BG000

**Value:** 1

**Group ID:** BG001

**Value:** 9

**Group ID:** BG002

**Value:** 5

**Group ID:** BG003

**Value:** 15

**Units:** Participants

### Group

**ID:** BG000

**Title:** ECMO Alone

**Description:** Patients receiving oseltamivir and Extracorporeal Membrane Oxygenation (ECMO) therapy

### Group

**ID:** BG001

**Title:** CVVHD Alone

**Description:** Patients receiving Continuous Venovenous Hemodialysis(CVVHD) and oseltamivir

### Group

**ID:** BG002

**Title:** CVVHD + ECMO

**Description:** Patient receiving oseltamivir and ECMO and CVVHD

### Group

**ID:** BG003

**Title:** Total

**Description:** Total of all reporting groups

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 1

#### Measurement

**Group ID:** BG002

**Value:** 1

#### Measurement

**Group ID:** BG003

**Value:** 2

**Category Title:** <=18 years

#### Measurement

**Group ID:** BG000

**Value:** 1

#### Measurement

**Group ID:** BG001

**Value:** 8

#### Measurement

**Group ID:** BG002

**Value:** 4

#### Measurement

**Group ID:** BG003

**Value:** 13

**Category Title:** Between 18 and 65 years

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 0

#### Measurement

**Group ID:** BG002

**Value:** 0

#### Measurement

**Group ID:** BG003

**Value:** 0

**Category Title:** >=65 years

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Spread:** 0

**Value:** 48

#### Measurement

**Group ID:** BG001

**Spread:** 10.2

**Value:** 33.0

#### Measurement

**Group ID:** BG002

**Spread:** 16.1

**Value:** 32.2

#### Measurement

**Group ID:** BG003

**Spread:** 12.4

**Value:** 33.8

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 0

#### Measurement

**Group ID:** BG001

**Value:** 3

#### Measurement

**Group ID:** BG002

**Value:** 1

#### Measurement

**Group ID:** BG003

**Value:** 4

**Category Title:** Female

#### Measurement

**Group ID:** BG000

**Value:** 1

#### Measurement

**Group ID:** BG001

**Value:** 6

#### Measurement

**Group ID:** BG002

**Value:** 4

#### Measurement

**Group ID:** BG003

**Value:** 11

**Category Title:** Male

**Class Title:** 

### Measure

#### Measurement

**Group ID:** BG000

**Value:** 1

#### Measurement

**Group ID:** BG001

**Value:** 9

#### Measurement

**Group ID:** BG002

**Value:** 5

#### Measurement

**Group ID:** BG003

**Value:** 15

**Class Title:** United States

**Denomination Units Selected:** 

## Results Section - Baseline Characteristics Module

### Measure 1
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Age, Categorical
**Unit of Measure:** Participants
### Measure 2
**Dispersion Type:** STANDARD_DEVIATION
**Parameter Type:** MEAN
**Title:** Age Continuous
**Unit of Measure:** years
### Measure 3
**Parameter Type:** COUNT_OF_PARTICIPANTS
**Title:** Sex: Female, Male
**Unit of Measure:** Participants
### Measure 4
**Parameter Type:** NUMBER
**Title:** Region of Enrollment
**Unit of Measure:** participants
## Results Section - More Information Module
### Certain Agreement
### Point of Contact
**Email:** muellerb@umich.edu
**Organization:** University of Michigan
**Phone:** 7346154578
**Title:** Bruce A. Mueller
## Results Section - Outcome Measures Module
### Outcome Measure 1
### Outcome Measure 2
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG000
- **Lower Limit:** 
- **Spread:** 8.0
- **Upper Limit:** 
- **Value:** 52.2
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 6.7
- **Upper Limit:** 
- **Value:** 43.3
**Title:** 
#### Outcome Measure 2
**Class:**
##### Category
**Measurements:**
- **Comment:** 
- **Group ID:** OG001
- **Lower Limit:** 
- **Spread:** 0.101
- **Upper Limit:** 
- **Value:** -0.008
- **Comment:** 
- **Group ID:** OG002
- **Lower Limit:** 
- **Spread:** 0.082
- **Upper Limit:** 
- **Value:** -0.033
**Title:** 
## Results Section
### Outcome Measures Module
#### Outcome Measure 1
**Description:** Oseltamivir Carboxylate Transmembrane Clearance by Continuous Venovenous Hemodialysis (Reported in mL/min).
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Population Description:** One patient in the CVVHD Alone group was excluded from the analysis because not enough data points were available for pharmacokinetic modeling.
**Reporting Status:** POSTED
**Time Frame:** 12 hours
**Title:** Continuous Venovenous Hemodialysis (CVVHD)Oseltamivir Carboxylate Transmembrane Clearance
**Type:** PRIMARY
**Unit of Measure:** mL/min
##### Group
**Description:** Patients receiving Continuous Venovenous Hemodialysis(CVVHD) and oseltamivir
**ID:** OG000
**Title:** CVVHD Alone
##### Group
**Description:** Patients receiving oseltamivir and ECMO and CVVHD
**ID:** OG001
**Title:** CVVHD + ECMO
##### Group
**Description:** Patients receiving ECMO only
**ID:** OG002
**Title:** ECMO Alone
#### Outcome Measure 2
**Description:** Mean percent change in oseltamivir carboxylate concentration pre- and post-oxygenator.
**Dispersion Type:** Standard Deviation
**Parameter Type:** MEAN
**Population Description:** All of the patients that received ECMO were included. Patients receiving CVVHD Alone did not receive ECMO and were not included.
**Reporting Status:** POSTED
**Time Frame:** 12 hours
**Title:** Oseltamivir Carboxylate Removal by ECMO
**Type:** PRIMARY
**Unit of Measure:** percent change in concentration
##### Group
**Description:** Patients receiving Continuous Venovenous Hemodialysis(CVVHD) and oseltamivir
**ID:** OG000
**Title:** CVVHD Alone
##### Group
**Description:** Patients receiving oseltamivir and ECMO and CVVHD
**ID:** OG001
**Title:** CVVHD + ECMO
##### Group
**Description:** Patients receiving ECMO only
**ID:** OG002
**Title:** ECMO Alone
### Participant Flow Module
#### Group
**Description:** Patients receiving oseltamivir and Extracorporeal Membrane Oxygenation (ECMO) therapy
**ID:** FG000
**Title:** ECMO Alone
#### Group
**Description:** Patients receiving Continuous Venovenous Hemodialysis(CVVHD) and oseltamivir
**ID:** FG001
**Title:** CVVHD Alone
#### Group
**Description:** Patient receiving oseltamivir and ECMO and CVVHD
**ID:** FG002
**Title:** CVVHD + ECMO
#### Period
**Title:** Overall Study
##### Milestone
**Type:** STARTED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 1
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 9
###### Achievement
**Group ID:** FG002
**Number of Subjects:** 5
##### Milestone
**Type:** COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 1
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 9
###### Achievement
**Group ID:** FG002
**Number of Subjects:** 5
##### Milestone
**Type:** NOT COMPLETED
###### Achievement
**Group ID:** FG000
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG001
**Number of Subjects:** 0
###### Achievement
**Group ID:** FG002
**Number of Subjects:** 0
**Has Results:** True