HyponatremiaPhase 4NCT00435591

A Study of Multiple Dosing Regimens of IV Conivaptan in Subjects With Euvolemic or Hypervolemic Hyponatremia

A Phase 4 study testing Conivaptan in people with Hyponatremia and Euvolemia, run by Cumberland Pharmaceuticals at 18 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The study will evaluate the effectiveness and safety of multiple dosing regimens of IV conivaptan in subjects with euvolemic or hypervolemic hyponatremia Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hyponatremia, Euvolemia, Hypervolemia
What is being tested?: Conivaptan
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 121 participants
Where: 18 sitesin 3 countries
Study dates: Jan 2007to Sep 2008
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subject has a serum sodium value between 115 and 133 mEq/L
Subject is euvolemic or hypervolemic

Who cannot join

Clinical evidence of volume depletion or dehydration
Uncontrolled brady- or tachyarrhythmias requiring emergent pacemaker placement or treatment

Trial locations and contacts

18 sites in 3 countries.

Country

City, postcode or hospital

18 sites in 3 countries

Israel12 sites

Study site
Afula, 18101
Study site
Ashkelon, 78308
Study site
Haifa, 31048
Study site
Haifa, 34362
Study site
Holon, 58100
Study site
Jerusalem, 910301
Study site
Jerusalem, 91120
Study site
Rehovot, 76100
Study site
Safed, 13100
Study site
Tel Aviv, 64239
Study site
Tel HaShomer, 52621
Study site
Tsrifin, 70300

Other trials in Israel

India5 sites

Study site
Bangalore, 560034
Study site
Bangalore, 560099
Study site
Bhopal, 462001
Study site
Hyderabaad, 500482
Study site
Karnāl, 132001

Other trials in India

United States1 site

Study site
Charleston, South Carolina, 29425

Other trials in United States

About this study

Official title: A Phase 4, Randomized, Parallel Group, Multi-Center Study to Assess the Safety and Efficacy of Multiple Dosing Regimens of IV Conivaptan in Subjects With Euvolemic or Hypervolemic Hyponatremia

The study will evaluate the effectiveness and safety of multiple dosing regimens of IV conivaptan in subjects with euvolemic or hypervolemic hyponatremia

Conditions: Hyponatremia, Euvolemia, Hypervolemia
Being tested: Conivaptan, placebo
Keywords: Hyponatremia, Euvolemia, Hypervolemia, Conivaptan, Vaprisol®, YM087
Medical subject headings: Hyponatremia, Edema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ConivaptanDrug
Also called YM087, Vaprisol
ampoule or premix bag
placeboDrug
ampoule or premix bag

Study groups in NCT00435591
Study group	Role	What they receive
Dose Regimen 1	Experimental	Placebo loading dose + 20mg/day continuous infusion conivaptan per ampoule Receives: Drug: Conivaptan; Drug: placebo
Dose Regimen 2	Experimental	Conivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule Receives: Drug: Conivaptan
Dose Regimen 3	Experimental	Placebo loading dose + 20mg/day continuous infusion conivaptan per premix bag Receives: Drug: Conivaptan; Drug: placebo
Dose Regimen 4	Experimental	Conivaptan loading dose (20mg) + 20mg/day continuous infusion conivaptan per premix bag Receives: Drug: Conivaptan

What is being measured

The primary outcome is the main question the study is designed to answer.

Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2
Infusion Site Reaction (ISR) was any local event other than isolated pain, bleeding, or bruising at the site of infusion.
One ISRMS has been reported for each participant \& represents the most severe state of ISR for that participant.
ISR scale is a health care provider assessment of ISRs using the following modified 5 point reporting scale: 0= No new reaction; 1+=Infusion site erythema, infusion site pain, infusion site warmth; 2+= Infusion site edema; 3+=Phlebitis, venous induration; 4+=Thrombophlebitis, venous thrombosis, infusion site infection, infusion site cellulitis
Measured: 48 hours

Secondary outcomes (5)

Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period
Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
Change from Baseline is calculated as Time point minus Baseline.
Measured: Baseline at 4, 6, 10, 16, 24, 30, 40, 48.5 hours and 7 days post-treatment
Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours
AUCna t is calculated as the baseline-adjusted area under serum sodium levels for a duration of time 0 to time t.
Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
Measured: 24.5 hours, 48.5 hours and 96.5 hours
Time From the First Dose of Study Drug to a Confirmed > 4 mEq/L Increase From Baseline in Serum Sodium During the 48.5 Hour Treatment Period
The upper limits of the interquartile range were not estimable in three of the treatment arms. Only the "placebo loading dose + YM087 premix continuous infusion" arm will be reported.
Time is number of hours to reach an increase of exceeding 4 mEq/L from baseline serum sodium.
Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
Measured: 48.5 hours
Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours
Patients with confirmed serum sodium level exceeding 4 mEq/L increase from baseline.
Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
Measured: 0-24.5 hours, 0-48.5 hours and 0-96.5 hours
Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours
Patients with confirmed serum sodium level exceeding 6 mEq/L increase from baseline or confirmed normal serum sodium level exceeding 135 mEq/L.
Baseline serum sodium value is the average of 2 serum sodium values taken at least 4 hours apart on Day-1 and within 24 hours of Hour 0 in the Treatment Period.
Measured: 0-24.5 hours, 0-48.5 hours and 0-96.5 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2007Sep 2008

First posted15 Feb 2007 (estimated)
Study startJan 2007
Primary completionSep 2008
Study completionSep 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HyponatremiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 121 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00435591
Sponsor's protocol ID: 087-CL-084
Status last verified: Apr 2014
First submitted: 14 Feb 2007
Last updated: 15 May 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Kalra S, Efrati S, Arthur JM, Oliven A, Velez JC, McNutt BE, Klasen S, Abeyratne A. Effect of loading dose and formulation on safety and efficacy of conivaptan in treatment of euvolemic and hypervolemic hyponatremia. Am J Health Syst Pharm. 2011 Apr 1;68(7):590-8. doi: 10.2146/ajhp100243.
PubMed 21411800

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Systematic Use of DDAVP to Prevent Serum Sodium Overcorrection in Severe Hyponatremia
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Enrolling by invitationObservational study
International Multi-center Retrospective Study of Patients With Serum Sodium ≤110 mmol/L to Determine the Relationship Between Osmotic Demyelination Syndrome (ODS) and Rapid Correction of Hyponatremia
Hyponatremia Symptomatic, Osmotic Demyelination Syndrome
Active, not recruitingObservational study
Samsca Post-marketing General Drug Use-results Survey in Patients With Hyponatremia in SIADH
Antidiuretic Hormone, Inappropriate Secretion
Recruiting
Urea for Treatment of Hyponatremia in Patients With SIAD Unresponsive to Fluid Restriction
SIAD - Syndrome of Inappropriate Antidiuresis
Active, not recruitingObservational study
Hyponatremia - Complications, Prognosis, Epidemiology in Finnish Tertiary Care
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All Hyponatremia trials

Study at a glance

From the registry record, last updated by the sponsor on 15 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 4, Randomized, Parallel Group, Multi-Center Study to Assess the Safety and Efficacy of Multiple Dosing Regimens of IV Conivaptan in Subjects With Euvolemic or Hypervolemic Hyponatremia
ClinicalTrials.gov ID: NCT00435591
Acronym / sponsor ID: 087-CL-084
Conditions: Hyponatremia, Euvolemia, Hypervolemia
Keywords: Hyponatremia, Euvolemia, Hypervolemia, Conivaptan, Vaprisol®, YM087
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 121 participants (actual)
Lead sponsor: Cumberland PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Jan 2007
Primary completion: Sep 2008 (actual)
Study completion: Sep 2008 (actual)
First posted: 15 Feb 2007 (estimated)
Results: Posted 26 May 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The study will evaluate the effectiveness and safety of multiple dosing regimens of IV conivaptan in subjects with euvolemic or hypervolemic hyponatremia

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Dose Regimen 1	Experimental	Drug: Conivaptan, Drug: placeboPlacebo loading dose + 20mg/day continuous infusion conivaptan per ampoule
Dose Regimen 2	Experimental	Drug: ConivaptanConivaptan loading dose (20mg)+ 20mg/day continuous infusion conivaptan per ampoule
Dose Regimen 3	Experimental	Drug: Conivaptan, Drug: placeboPlacebo loading dose + 20mg/day continuous infusion conivaptan per premix bag
Dose Regimen 4	Experimental	Drug: ConivaptanConivaptan loading dose (20mg) + 20mg/day continuous infusion conivaptan per premix bag

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Subject has a serum sodium value between 115 and 133 mEq/L
Subject is euvolemic or hypervolemic

Key exclusion criteria (2 listed)

Clinical evidence of volume depletion or dehydration
Uncontrolled brady- or tachyarrhythmias requiring emergent pacemaker placement or treatment

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ConivaptanAlso: YM087, Vaprisolampoule or premix bag	Drug	Dose Regimen 1, Dose Regimen 2, Dose Regimen 3, Dose Regimen 4
placeboampoule or premix bag	Drug	Dose Regimen 1, Dose Regimen 3

Primary outcome

Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2
Time frame: 48 hours
Infusion Site Reaction (ISR) was any local event other than isolated pain, bleeding, or bruising at the site of infusion. One ISRMS has been reported for each participant \& represents the most severe state of ISR for that participant. ISR scale is a health care provider assessment of ISRs using the following modified 5 point reporting scale: 0= No new reaction; 1+=Infusion site erythema, infusion site pain, infusion site warmth; 2+= Infusion site edema; 3+=Phlebitis, venous induration; 4+=Thrombophlebitis, venous thrombosis, infusion site infection, infusion site cellulitis

5 secondary outcomes

Change From Baseline in Serum Sodium at Each Time Point Over the Duration of the Treatment Period and 7-day Post Treatment Period
Time frame: Baseline at 4, 6, 10, 16, 24, 30, 40, 48.5 hours and 7 days post-treatment
Baseline Adjusted Area Under the Concentration - Time Curve (AUC) in Serum Sodium Over the Duration of the First 24.5 Hours, the First 48.5 Hours, and the First 96.5 Hours
Time frame: 24.5 hours, 48.5 hours and 96.5 hours
Time From the First Dose of Study Drug to a Confirmed > 4 mEq/L Increase From Baseline in Serum Sodium During the 48.5 Hour Treatment Period
Time frame: 48.5 hours
Number of Patients With Confirmed Serum Sodium Level Exceeding 4 mEq/L Increase From Baseline Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours
Time frame: 0-24.5 hours, 0-48.5 hours and 0-96.5 hours
Number of Patients With Confirmed Serum Sodium Level Exceeding 6 mEq/L Increase From Baseline or Confirmed Normal Serum Sodium Level Exceeding 135 mEq/L Over the Duration 0-24.5 Hours, 0-48.5 Hours, and 0-96.5 Hours
Time frame: 0-24.5 hours, 0-48.5 hours and 0-96.5 hours

Results and safety

Results posted to the registry on 26 May 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose Regimen 1	30	23
Dose Regimen 2	31	27
Dose Regimen 3	30	25
Dose Regimen 4	30	19

Primary outcome: Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2

Time frame: 48 hours. Number. Unit: Participants

Measure	Dose Regimen 1 n = 28	Dose Regimen 2 n = 30
Infusion Site Reaction - No assessment	0	1
Infusion Site Reaction - 0	17	16
Infusion Site Reaction - 1+	5	7
Infusion Site Reaction - 2+	2	0
Infusion Site Reaction - 3+	4	5
Infusion Site Reaction - 4+	0	1

Dose Regimen 1 vs Dose Regimen 2: Least Squares Mean Difference: 0.23 (95% CI -0.37 to 0.83)

Population analysed: Population is Safety Analysis Set (SAF): All randomized patients who received at least 1 dose of study drug. The number of participants per arm is consistent for all categories of the data table.

5 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dose Regimen 1	2 of 28 (7.1%)	6 of 28 (21.4%)	Not reported
Dose Regimen 2	5 of 30 (16.7%)	12 of 30 (40%)	Not reported
Dose Regimen 3	8 of 30 (26.7%)	4 of 30 (13.3%)	Not reported
Dose Regimen 4	2 of 29 (6.9%)	8 of 29 (27.6%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21411800Kalra S, Efrati S, Arthur JM, Oliven A, Velez JC, McNutt BE, Klasen S, Abeyratne A. Effect of loading dose and formulation on safety and efficacy of conivaptan in treatment of euvolemic and hypervolemic hyponatremia. Am J Health Syst Pharm. 2011 Apr 1;68(7):590-8. doi: 10.2146/ajhp100243.
Link to Prescribing InformationLink provided by the sponsor.

Related trials for Hyponatremia

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Enrolling by invitationObservational study
International Multi-center Retrospective Study of Patients With Serum Sodium ≤110 mmol/L to Determine the Relationship Between Osmotic Demyelination Syndrome (ODS) and Rapid Correction of Hyponatremia
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Active, not recruitingObservational study
Samsca Post-marketing General Drug Use-results Survey in Patients With Hyponatremia in SIADH
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Art Wheeler, MD study director

Cumberland Pharmaceuticals

18 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Conivaptan in people with Hyponatremia and Euvolemia, run by Cumberland Pharmaceuticals at 18 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Israel, India, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 May 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number and Severity of Infusion Site Reactions (ISRs) Using a Modified ISR Reporting Scale for Phlebitis and Infiltration in Patients Treated With Dose Regimen 1 and Dose Regimen 2 (time frame: 48 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00435591, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2014.