Trial Outcomes & Findings for Conivaptan for the Reduction of Cerebral Edema in Intracerebral Hemorrhage- A Safety and Tolerability Study (NCT NCT03000283)

NCT ID: NCT03000283

Last Updated: 2020-04-17

Results Overview

The number of participants with abnormal seizure activity and/or abnormal lab values and/or increase in infection rate and/or any drug-related adverse events.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 7 participants
• Primary outcome timeframe: Baseline to 168 hours post-enrollment
• Results posted on: 2020-04-17

Participant Flow

Participants were recruited based on physician referral at a single medical institution between March 1, 2017 and November 7, 2018. The first participant was enrolled on March 22, 2017 and the last participant was enrolled on November 7, 2018.

Participant milestones

Measure	Conivaptan Treatment Group All seven patients in this arm will receive conivaptan as described in Interventions. Conivaptan: Patients will receive 20mg IV of the study drug every 12 hours equaling 40mg/day over 2 days (4 doses total), in addition to the standardized ICH management targets using the PI's version of standardized ICH management targets.Usual standard of care can include sedation and analgesia as needed, elevation of the head of the bed, mannitol and/or saline as needed to reduce ICP, and temperature control with antipyretics such as acetaminophen. The conivaptan bolus (20mg), which is premixed with 100ml of 5% dextrose in water, is infused (peripherally) over 30 minutes, most commonly through an already placed central line.
Overall Study STARTED	7
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Conivaptan for the Reduction of Cerebral Edema in Intracerebral Hemorrhage- A Safety and Tolerability Study

Baseline characteristics by cohort

Measure	Conivaptan Treatment Group n=7 Participants All seven patients in this arm will receive conivaptan as described in Interventions. Conivaptan: Patients will receive 20mg IV of the study drug every 12 hours equaling 40mg/day over 2 days (4 doses total), in addition to the standardized ICH management targets using the PI's version of standardized ICH management targets.Usual standard of care can include sedation and analgesia as needed, elevation of the head of the bed, mannitol and/or saline as needed to reduce ICP, and temperature control with antipyretics such as acetaminophen. The conivaptan bolus (20mg), which is premixed with 100ml of 5% dextrose in water, is infused (peripherally) over 30 minutes, most commonly through an already placed central line.
Age, Continuous	58.5 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 168 hours post-enrollment

The number of participants with abnormal seizure activity and/or abnormal lab values and/or increase in infection rate and/or any drug-related adverse events.

Outcome measures

Measure	Conivaptan Treatment Group n=7 Participants All seven patients in this arm will receive conivaptan as described in Interventions. Conivaptan: Patients will receive 20mg IV of the study drug every 12 hours equaling 40mg/day over 2 days (4 doses total), in addition to the standardized ICH management targets using the PI's version of standardized ICH management targets.Usual standard of care can include sedation and analgesia as needed, elevation of the head of the bed, mannitol and/or saline as needed to reduce ICP, and temperature control with antipyretics such as acetaminophen. The conivaptan bolus (20mg), which is premixed with 100ml of 5% dextrose in water, is infused (peripherally) over 30 minutes, most commonly through an already placed central line.
Patient Tolerance of Conivaptan Abnormal Seizure Activity	0 Participants
Patient Tolerance of Conivaptan Abnormal Lab Values	0 Participants
Patient Tolerance of Conivaptan Infections	1 Participants
Patient Tolerance of Conivaptan Drug-related Adverse Events	0 Participants

SECONDARY outcome

Timeframe: Enrollment through hospital discharge, up to 3 weeks

All-cause deaths during hospitalization

Outcome measures

Measure

Conivaptan Treatment Group n=7 Participants All seven patients in this arm will receive conivaptan as described in Interventions. Conivaptan: Patients will receive 20mg IV of the study drug every 12 hours equaling 40mg/day over 2 days (4 doses total), in addition to the standardized ICH management targets using the PI's version of standardized ICH management targets.Usual standard of care can include sedation and analgesia as needed, elevation of the head of the bed, mannitol and/or saline as needed to reduce ICP, and temperature control with antipyretics such as acetaminophen. The conivaptan bolus (20mg), which is premixed with 100ml of 5% dextrose in water, is infused (peripherally) over 30 minutes, most commonly through an already placed central line.

In-hospital Mortality

0 Participants

SECONDARY outcome

Timeframe: Baseline to 168 hours post-enrollment

Changes in cerebral edema (CE) as measured on CT. Goal is a -5 to -10% change in CE over time. Change will be measured both as absolute change in volume, calculated as the final volume minus the baseline volume measure and converted to a percentage of the baseline volume measure.

Outcome measures

Measure

Conivaptan Treatment Group n=7 Participants All seven patients in this arm will receive conivaptan as described in Interventions. Conivaptan: Patients will receive 20mg IV of the study drug every 12 hours equaling 40mg/day over 2 days (4 doses total), in addition to the standardized ICH management targets using the PI's version of standardized ICH management targets.Usual standard of care can include sedation and analgesia as needed, elevation of the head of the bed, mannitol and/or saline as needed to reduce ICP, and temperature control with antipyretics such as acetaminophen. The conivaptan bolus (20mg), which is premixed with 100ml of 5% dextrose in water, is infused (peripherally) over 30 minutes, most commonly through an already placed central line.

Change in Cerebral Edema

-37.1 percentage of change from baseline Interval -96.2 to 70.7

SECONDARY outcome

Timeframe: Enrollment through hospital discharge, up to 3 weeks

Cost as measured by length of stay in the neuro ICU.

Outcome measures

Measure

Conivaptan Treatment Group n=7 Participants All seven patients in this arm will receive conivaptan as described in Interventions. Conivaptan: Patients will receive 20mg IV of the study drug every 12 hours equaling 40mg/day over 2 days (4 doses total), in addition to the standardized ICH management targets using the PI's version of standardized ICH management targets.Usual standard of care can include sedation and analgesia as needed, elevation of the head of the bed, mannitol and/or saline as needed to reduce ICP, and temperature control with antipyretics such as acetaminophen. The conivaptan bolus (20mg), which is premixed with 100ml of 5% dextrose in water, is infused (peripherally) over 30 minutes, most commonly through an already placed central line.

Cost

14.4 days Interval 9.7 to 28.9

SECONDARY outcome

Timeframe: Baseline to 168 hours post-enrollment

Cost as measured by:

1. Need for external ventricular drain (EVD)/bolt or surgical procedures (craniectomy, clot evacuation,VPS) for reduction/management of CE.

2. Need for central venous lines, arterial lines, peripherally inserted central venous catheter (PICC) lines, tracheostomy/percutaneous endoscopic gastrostomies (PEGs).

3. Number of patients requiring a ventilator.

Outcome measures

Measure	Conivaptan Treatment Group n=7 Participants All seven patients in this arm will receive conivaptan as described in Interventions. Conivaptan: Patients will receive 20mg IV of the study drug every 12 hours equaling 40mg/day over 2 days (4 doses total), in addition to the standardized ICH management targets using the PI's version of standardized ICH management targets.Usual standard of care can include sedation and analgesia as needed, elevation of the head of the bed, mannitol and/or saline as needed to reduce ICP, and temperature control with antipyretics such as acetaminophen. The conivaptan bolus (20mg), which is premixed with 100ml of 5% dextrose in water, is infused (peripherally) over 30 minutes, most commonly through an already placed central line.
Cost EVD/bolt or surgical procedures	0 Participants
Cost Lines or tracheostomy/PEG	7 Participants
Cost Ventilator	1 Participants

SECONDARY outcome

Timeframe: At discharge from ICU and from hospital, up to 3 weeks

Modified Rankin Scale (0 to 6) at discharge from the hospital. A score of 0 indicates no disability and a score of 6 indicates the patient died. Functional independence is defined as a score of 2 or less.

Outcome measures

Measure

Conivaptan Treatment Group n=7 Participants All seven patients in this arm will receive conivaptan as described in Interventions. Conivaptan: Patients will receive 20mg IV of the study drug every 12 hours equaling 40mg/day over 2 days (4 doses total), in addition to the standardized ICH management targets using the PI's version of standardized ICH management targets.Usual standard of care can include sedation and analgesia as needed, elevation of the head of the bed, mannitol and/or saline as needed to reduce ICP, and temperature control with antipyretics such as acetaminophen. The conivaptan bolus (20mg), which is premixed with 100ml of 5% dextrose in water, is infused (peripherally) over 30 minutes, most commonly through an already placed central line.

Modified Rankin Scale (mRS) Score

5 score on a scale Interval 3.0 to 5.0

Adverse Events

Conivaptan Treatment Group

Serious events: 7 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Conivaptan Treatment Group n=7 participants at risk All seven patients in this arm will receive conivaptan as described in Interventions. Conivaptan: Patients will receive 20mg IV of the study drug every 12 hours equaling 40mg/day over 2 days (4 doses total), in addition to the standardized ICH management targets using the PI's version of standardized ICH management targets.Usual standard of care can include sedation and analgesia as needed, elevation of the head of the bed, mannitol and/or saline as needed to reduce ICP, and temperature control with antipyretics such as acetaminophen. The conivaptan bolus (20mg), which is premixed with 100ml of 5% dextrose in water, is infused (peripherally) over 30 minutes, most commonly through an already placed central line.
Nervous system disorders Intracranial Hemorrhage Expansion	14.3% 1/7 • Throughout study participation. For each patient this extended from enrollment to 3 months after enrollment.
Respiratory, thoracic and mediastinal disorders Pulmonary Edema	28.6% 2/7 • Throughout study participation. For each patient this extended from enrollment to 3 months after enrollment.
Infections and infestations Urinary Tract Infection	14.3% 1/7 • Throughout study participation. For each patient this extended from enrollment to 3 months after enrollment.
Surgical and medical procedures Catheterization, Central Venous (PICC)	100.0% 7/7 • Throughout study participation. For each patient this extended from enrollment to 3 months after enrollment.
Surgical and medical procedures Tracheostomy	42.9% 3/7 • Throughout study participation. For each patient this extended from enrollment to 3 months after enrollment.
Surgical and medical procedures Gastostomy (PEG)	28.6% 2/7 • Throughout study participation. For each patient this extended from enrollment to 3 months after enrollment.
Nervous system disorders Increase in Cerebral Edema	14.3% 1/7 • Throughout study participation. For each patient this extended from enrollment to 3 months after enrollment.
Vascular disorders Deep Vein Thrombosis	28.6% 2/7 • Throughout study participation. For each patient this extended from enrollment to 3 months after enrollment.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Jesse Corry

Allina Health

Phone: 651-241-6550

Email: Jesse.Corry@allina.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place