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CompletedNCT00478192Updated May 15, 2014Results posted

Study of Efficacy & Safety for 3 Infusion Regimens of IV Conivaptan in Subjects With Euvolemic or Hypervolemic Hyponatremia

A Phase 3 interventional study of Conivaptan and Placebo in Hyponatremia, sponsored by Cumberland Pharmaceuticals. Completed at 26 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-05-15.

Sponsored by Cumberland Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
50
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The study is designed to assess the efficacy and safety of multiple infusions of conivaptan in subjects with euvolemic or hypervolemic hyponatremia

02

Conditions studied

  • Hyponatremia

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Keywords

  • hyponatremia
  • hypervolemic
  • euvolemic
  • edematous
  • conivaptan
03

In context

Hyponatremia

155 studies on the registry are indexed under Hyponatremia; 17 are open to participants now.

This study's enrollment of 50 is below the median of 58 across 92 interventional studies indexed under Hyponatremia.

Browse Hyponatremia studies →

Lead sponsor

Cumberland Pharmaceuticals is the lead sponsor of 47 studies on the registry; 1 is open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 5 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Euvolemic or hypervolemic (edematous) based on clinical presentation
  • Serum sodium between 115 and 130mEq/L at baseline

Exclusion criteria

Exclusion Criteria:

  • Clinical presentation of volume depletion or dehydration
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
50 participants (actual)

Study arms

  • Experimental
    Regimen 1 Conivaptan QD

    20 mg conivaptan once a day

    Drug: Conivaptan

  • Experimental
    Regimen 2 Conivaptan BID

    20 mg conivaptan two times a day

    Drug: Conivaptan

  • Placebo comparator
    Regimen 3 Placebo

    Drug: Placebo

Interventions

  • DrugConivaptan

    premix bag

    Also known as: YM087, Vaprisol

  • DrugPlacebo

    premix bag

06

What researchers measure

Primary outcomes

  1. Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation.

    Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Hour 48 - Baseline.

    Time frame: Baseline and 48 hours

Secondary outcomes

  1. Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment

    Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Actual Data for each time point - Baseline

    Time frame: Baseline, Hour 4, Hour 12, Hour 16, Hour 24, Hour 28, Hour 36, Hour 40 and Hour 48

  2. Time From the First Dose of Study Medication to a Confirmed >4 mEq/L Increase From Baseline in Serum Sodium

    Confirmed sodium levels refers to two consecutive increases from baseline in sodium of \>4 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. The endpoint was not evaluable in the placebo arm (median and interquartile range cannot be estimated) or the conivaptan QD arm (interquartile range cannot be estimated) because too high a percentage of patients were censored for the event. Only the conivaptan BID arm will be reported.

    Time frame: 48 Hours

  3. Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours

    Confirmed sodium levels refers to two consecutive increases from baseline in sodium of \>4 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1.

    Time frame: 48 Hours

  4. Number of Patients With Confirmed Serum Sodium Level Increase >6 mEq/L From Baseline or Confirmed Normal Serum Sodium Level (>135 mEq/L) Over the Duration 0 to 48 Hours

    Confirmed sodium levels refers to two consecutive increases from baseline in sodium of \>6 mEq/L or two consecutive measurements \>135 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1.

    Time frame: 48 Hours

  5. Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours

    Each individual subject's change from baseline serum sodium levels was used to calculate baseline adjusted area under the curve serum sodium levels for a duration of Time 0 to Time t in hours (labeled as AUC(Na)(0-t). The last available serum sodium level prior to dosing on Day 1 was used as baseline. "t"=48 Hours

    Time frame: 48 Hours

  6. Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment

    Effective water clearence (EWC) was calculated as EWC=V(1-(Una+Uk)/(Pna+Pk)), where V is urine volume, Una is the urine sodium concentration, Uk is the urine potassium concentration, Pna is the serum/plasma sodium concentration, an Pk is the serum /plasma potassium concentration. Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Actual Data for each time point - Baseline

    Time frame: Baseline, Hour 12, Hour 24,Hour 36 and Hour 48

  7. Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment

    Free water clearance (FWC) was calculated as FWC=V(1-Uosm/Posm), where V is urine volume, Uosm is the urine osmolality, Posm is the plasma sodium osmolality. Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Actual Data for each time point - Baseline

    Time frame: Baseline, Hour 24 and Hour 48

07

Results

Posted Apr 21, 2010
Limitations and caveats
Company makes no warranties or representations of any kind as to the currency or completeness of the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose and shall not be liable for any damages.

Participant flow

Participant flow — Overall Study
MilestoneRegimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 Placebo
Started202010
Full analysis set / safety analysis set20209
End of treatment18168
Completed16158
Not completed452

Outcome measures

PrimaryChange in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation.

Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Hour 48 - Baseline.

Time frame:
Baseline and 48 hours
Reported as:
Mean · mEq/L
Change in Serum Sodium From Baseline to the 48 Hour Assessment or Study Drug Discontinuation.
mEq/LRegimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 Placebo
Baseline (N= 20; 20; 9)126.03 ± 4.017126.39 ± 3.581125.55 ± 3.648
Hour 48 (N=19; 17; 8)130.4 ± 5.21133.4 ± 4.82127.6 ± 2.36
Change from Baseline (N=19; 17; 8)4.00 ± 3.807.36 ± 4.041.16 ± 2.86
Statistical analysis
  • Regimen 1 Conivaptan QD vs Regimen 2 Conivaptan BID · ANCOVA · p = 0.028 (P-Values are not adjusted on the basis of multiple comparrisons)
  • Regimen 1 Conivaptan QD vs Regimen 3 Placebo · ANCOVA · p = 0.019 (P-Values are not adjusted on the basis of multiple comparrisons)
  • Regimen 2 Conivaptan BID vs Regimen 3 Placebo · ANCOVA · p = <0.001 (P-Values are not adjusted on the basis of multiple comparrisons)
SecondaryChange From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment

Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Actual Data for each time point - Baseline

Time frame:
Baseline, Hour 4, Hour 12, Hour 16, Hour 24, Hour 28, Hour 36, Hour 40 and Hour 48
Reported as:
Mean · mEq/L
Change From Baseline in Serum Sodium Level at Each Time Point Through the 48 Hour Assessment
mEq/LRegimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 Placebo
Baseline (N=20; 20; 9)126.03 ± 4.02126.39 ± 3.58125.55 ± 3.65
Hour 4 (N=19; 20; 8)128.03 ± 4.62128.47 ± 4.21125.80 ± 4.63
Change at Hour 4 (N=19; 20; 8)1.59 ± 2.322.08 ± 2.65-0.63 ± 2.77
Hour 12 (N=19; 19; 7)128.22 ± 5.27130.85 ± 5.88127.21 ± 5.24
Change at Hour 12 (N=19; 19; 7)1.78 ± 3.444.65 ± 4.060.73 ± 3.92
Hour 16 (N=19; 17; 7)129.34 ± 4.51131.04 ± 5.07127.57 ± 3.78
Change at Hour 16 (N=19; 17; 7)2.90 ± 3.464.93 ± 3.281.09 ± 2.69
Hour 24 (N=18; 16; 8)128.87 ± 4.73130.74 ± 5.33127.48 ± 3.62
Change at Hour 24 (N=18; 16; 8)2.66 ± 3.764.62 ± 3.591.05 ± 2.73
Hour 28 (N=19; 17; 8)130.79 ± 4.94131.62 ± 4.52126.49 ± 4.03
Change at Hour 28 (N=19; 17; 8)4.35 ± 3.805.51 ± 2.750.06 ± 3.30
Hour 36 (N=19; 15; 8)131.42 ± 4.99132.47 ± 5.04127.31 ± 3.05
Change at Hour 36 (N=19; 15; 8)4.98 ± 3.736.54 ± 3.280.89 ± 2.55
Hour 40 (N=19; 16; 8)130.83 ± 5.04132.23 ± 3.99127.00 ± 1.85
Change at Hour 40 (N=19; 16; 8)4.39 ± 3.446.30 ± 3.270.58 ± 1.66
Hour 48 (N=19; 17; 8)130.44 ± 5.21133.35 ± 4.82127.59 ± 2.36
Change at Hour 48 (N=19; 17; 8)4.00 ± 3.807.36 ± 4.041.16 ± 2.86
SecondaryTime From the First Dose of Study Medication to a Confirmed >4 mEq/L Increase From Baseline in Serum Sodium

Confirmed sodium levels refers to two consecutive increases from baseline in sodium of \>4 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. The endpoint was not evaluable in the placebo arm (median and interquartile range cannot be estimated) or the conivaptan QD arm (interquartile range cannot be estimated) because too high a percentage of patients were censored for the event. Only the conivaptan BID arm will be reported.

Time frame:
48 Hours
Reported as:
Median · Hours
Time From the First Dose of Study Medication to a Confirmed >4 mEq/L Increase From Baseline in Serum Sodium
HoursRegimen 2 Conivaptan BID
Time From the First Dose of Study Medication to a Confirmed >4 mEq/L Increase From Baseline in Serum Sodium16.43 (12.00 to 32.00)
SecondaryNumber of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours

Confirmed sodium levels refers to two consecutive increases from baseline in sodium of \>4 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1.

Time frame:
48 Hours
Reported as:
Number · Patients
Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours
PatientsRegimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 Placebo
Number of Patients With Confirmed Serum Sodium Level > 4 mEq/L Increase From Baseline Over 0 to 48 Hours12172
SecondaryNumber of Patients With Confirmed Serum Sodium Level Increase >6 mEq/L From Baseline or Confirmed Normal Serum Sodium Level (>135 mEq/L) Over the Duration 0 to 48 Hours

Confirmed sodium levels refers to two consecutive increases from baseline in sodium of \>6 mEq/L or two consecutive measurements \>135 mEq/L; baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1.

Time frame:
48 Hours
Reported as:
Number · Patients
Number of Patients With Confirmed Serum Sodium Level Increase >6 mEq/L From Baseline or Confirmed Normal Serum Sodium Level (>135 mEq/L) Over the Duration 0 to 48 Hours
PatientsRegimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 Placebo
Number of Patients With Confirmed Serum Sodium Level Increase >6 mEq/L From Baseline or Confirmed Normal Serum Sodium Level (>135 mEq/L) Over the Duration 0 to 48 Hours6110
SecondaryBaseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours

Each individual subject's change from baseline serum sodium levels was used to calculate baseline adjusted area under the curve serum sodium levels for a duration of Time 0 to Time t in hours (labeled as AUC(Na)(0-t). The last available serum sodium level prior to dosing on Day 1 was used as baseline. "t"=48 Hours

Time frame:
48 Hours
Reported as:
Mean · Hour * mEq/L
Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours
Hour * mEq/LRegimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 Placebo
Baseline -Adjusted Area Under the Curve (AUC) in Serum Sodium Over the Duration 0 to 48 Hours142.72 ± 132.94244.17 ± 142.6423.21 ± 91.49
Statistical analysis
  • Regimen 1 Conivaptan QD vs Regimen 2 Conivaptan BID · ANCOVA · p = 0.079
SecondaryChange From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment

Effective water clearence (EWC) was calculated as EWC=V(1-(Una+Uk)/(Pna+Pk)), where V is urine volume, Una is the urine sodium concentration, Uk is the urine potassium concentration, Pna is the serum/plasma sodium concentration, an Pk is the serum /plasma potassium concentration. Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Actual Data for each time point - Baseline

Time frame:
Baseline, Hour 12, Hour 24,Hour 36 and Hour 48
Reported as:
Mean · mL
Change From Baseline in Effective Water Clearance (EWC) at Each Time Point Through the 48-hour Assessment
mLRegimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 Placebo
Baseline (N=16; 12; 6)6.76 ± 47.9139.86 ± 245.2318.66 ± 45.05
Hour 12 (N=14; 12; 5)355.65 ± 684.35405.21 ± 744.88136.22 ± 154.94
Change at Hour 12 (N=12;12; 4)301.52 ± 671.78365.35 ± 699.96135.44 ± 123.36
Hour 24 (N=14; 12; 6)-50.19 ± 794.22-261.27 ± 1009.24368.01 ± 688.81
Change at Hour 24 (N=13; 11; 5)-70.61 ± 796.01-391.76 ± 1206.39383.73 ± 723.33
Hour 36 (N=15; 11; 6)36.85 ± 905.1812.66 ± 743.24726.96 ± 1013.78
Change at Hour 36 (N=12; 8; 5)-91.07 ± 912.66-89.12 ± 805.36810.45 ± 1079.89
Hour 48 (N=14; 11; 5)-77.37 ± 1169.30-179.37 ± 852.58569.09 ± 1392.07
Change at Hour 48 (N=12; 10; 4)80.23 ± 1116.99-240.39 ± 759.82690.98 ± 2872.2
SecondaryChange From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment

Free water clearance (FWC) was calculated as FWC=V(1-Uosm/Posm), where V is urine volume, Uosm is the urine osmolality, Posm is the plasma sodium osmolality. Baseline is the average of the two most recent serum sodium levels prior to start of dosing on day 1. Hour 48: Hour 48 or time that ended study participation prior to the hour 48 assessment. Change is calculated as Actual Data for each time point - Baseline

Time frame:
Baseline, Hour 24 and Hour 48
Reported as:
Mean · mL
Change From Baseline in Free Water Clearance (FWC) at Each Time Point Through the 48-hour Assessment
mLRegimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 Placebo
Baseline (N=14; 11; 6)-53.87 ± 45.476.55 ± 165.07-34.90 ± 74.32
Hour 24 (N=14; 12; 6)-972.29 ± 1455.66-611.14 ± 693.863-416.71 ± 666.97
Change at Hour 24 (N=11; 10; 5)-936.99 ± 1618.46-513.33 ± 566.72-420.75 ± 747.84
Hour 48 (N=14;12; 5)-1243.39 ± 2211.22-769.19 ± 934.31-592.96 ± 1050.94
Change at Hour 48 (N=11; 10; 4)-1313.98 ± 2477.39-603.67 ± 761.90-702.11 ± 1117.92

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Regimen 1 Conivaptan QD—6/20 (30%)7/20 (35%)
Regimen 2 Conivaptan BID—5/20 (25%)10/20 (50%)
Regimen 3 Placebo—2/9 (22.2%)5/9 (55.6%)
Most frequent serious events
Showing 10 of 16
Most frequent serious events
EventRegimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 Placebo
IleusGastrointestinal disorders0/200/201/9
Clostridium difficile colitisInfections and infestations0/200/201/9
HyperkalaemiaMetabolism and nutrition disorders0/200/201/9
DeliriumPsychiatric disorders0/200/201/9
Renal failure acuteRenal and urinary disorders0/200/201/9
Cardiac failure congestiveCardiac disorders2/201/200/9
CoagulopathyBlood and lymphatic system disorders1/200/200/9
Multi-organ failureGeneral disorders1/200/200/9
PneumoniaInfections and infestations0/201/200/9
HyponatraemiaMetabolism and nutrition disorders1/200/200/9
Most frequent other events
Showing 10 of 60
Most frequent other events
EventRegimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 Placebo
FallInjury, poisoning and procedural complications0/200/202/9
HypotensionVascular disorders3/200/201/9
AnaemiaBlood and lymphatic system disorders2/201/201/9
Supraventricular tachycardiaCardiac disorders0/200/201/9
HypothyrodismEndocrine disorders0/200/201/9
Abdominal painGastrointestinal disorders1/200/201/9
Gastric haemorrhageGastrointestinal disorders0/200/201/9
Urinary tract infectionInfections and infestations0/202/201/9
Blood creatine phosphokinaise increasedInvestigations0/200/201/9
HyperglycaemiaMetabolism and nutrition disorders1/200/201/9

Baseline characteristics

Age, Continuous
Age, Continuous(years)Regimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 PlaceboTotal
Mean58.6 ± 17.3667.5 ± 14.7061.8 ± 20.1962.8 ± 17.01
Sex: Female, Male
Sex: Female, Male(Participants)Regimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 PlaceboTotal
Female711826
Male139123
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Regimen 1 Conivaptan QDRegimen 2 Conivaptan BIDRegimen 3 PlaceboTotal
Asian74314
Black or African American1124
White1215431
08

Study locations

26 sites
  • Huntsville, Alabama 35801, United States
  • Tucson, Arizona 85723, United States
  • Los Angeles, California 90073, United States
  • Denver, Colorado 80218, United States
  • Jacksonville, Florida 32216, United States
  • Port Charlotte, Florida 33952, United States
  • Chicago, Illinois 60612, United States
  • Indianapolis, Indiana 46260, United States
  • Hazard, Kentucky 41701, United States
  • Detroit, Michigan 48201, United States
  • Omaha, Nebraska 68198, United States
  • Bronx, New York 10461, United States
  • Cincinnati, Ohio 45267, United States
  • Fairfield, Ohio 45014, United States
  • Toledo, Ohio 43606, United States
  • Philadelphia, Pennsylvania 19102, United States
  • Philadelphia, Pennsylvania 19104, United States
  • Philadelphia, Pennsylvania 19107, United States
  • Philadelphia, Pennsylvania 19140, United States
  • Charleston, South Carolina 29425, United States
  • Orangeburg, South Carolina 29118, United States
  • Coimbatore, 641014, India
  • Indore, 452014, India
  • Jaipur, 302013, India
  • Karnal, 132001, India
  • Visakhapatnam, 530002, India
09

References and documents

Publications

  • Koren MJ, Hamad A, Klasen S, Abeyratne A, McNutt BE, Kalra S. Efficacy and safety of 30-minute infusions of conivaptan in euvolemic and hypervolemic hyponatremia. Am J Health Syst Pharm. 2011 May 1;68(9):818-27. doi: 10.2146/ajhp100260. Erratum In: Am J Health Syst Pharm. 2011 Aug 1;68(15):1374. PubMed 21515866 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 15, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00478192
Lead sponsor
Cumberland Pharmaceuticals
Responsible party
Sponsor
First posted
May 24, 2007
Start date
Apr 2007
Primary completion
Aug 2008
Completion
Aug 2008
Results posted
Apr 21, 2010
Last update
May 15, 2014

Study contacts

Art Wheeler, MD
study director · Cumberland Pharmaceuticals, Inc.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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