Intradialytic HypotensionPhase 2IDH201NCT00657046
Safety and Benefit Study of Droxidopa to Treat Patients With Intradialytic Hypotension
A Phase 2 study testing Droxidopa in people with Intradialytic Hypotension, run by Chelsea Therapeutics at 1 site in United States.
Trial summary
In clinical trials in Japan, droxidopa has been shown to be effective in affecting blood pressure changes upon orthostatic challenge in patients with autonomic dysfunction, as well as reducing the severity and frequency of symptoms of orthostatic hypotension in these patients. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Intradialytic Hypotension
- What is being tested?
- Droxidopa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2007to Jan 2009
- Phase
- Phase 2
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female and aged 18 years or over;
- Clinical diagnosis of ESRD;
- Demonstrated requirement to undergo maintenance HD 3 times per week for sessions at least 3 hours in duration;
- Medical history consistent with IDH existing for at least 1 month;
- Observed symptomatic intradialytic hypotension in 3 of 6 HD sessions during screening, as defined by as a decrease in systolic blood pressure by ≥20 mm Hg or a decrease in MAP by 10 mm Hg associated with symptoms that include: abdominal discomfort; yawning; sighing; nausea; vomiting; muscle cramps; restlessness; dizziness or fainting; and anxiety (definition according to: National Kidney Foundation 2007) ;
- Provide written informed consent to participate in the study and understand that they may withdraw their consent at any time without prejudice to their future medical care.
Who cannot join
- Currently taking ephedrine or midodrine;
- Patients taking ephedrine or midodrine may enroll after a minimum 7 day washout period
- Taking anti-hypertensive medication on the day of dialysis;
- Currently taking selective norepinephrine re-uptake inhibitors;
- Current known or suspected drug or substance abuse;
- Women of childbearing potential who are not using a medically accepted contraception;
Show all 23Show fewer
- Subject Restrictions:
- Reproductive potential: Female subjects should be either post-menopausal (amenorrhea for at least 12 consecutive months), surgically sterile, or women of child-bearing potential (WOCP) who are using or agree to use acceptable methods of contraception. Acceptable contraceptives include intrauterine devices (IUDs), hormonal contraceptives (oral, depot, patch or injectable) and double barrier methods such as condoms or diaphragms with spermicidal gel or foam.
- For WOCP a urine/serum beta HCG pregnancy test must be conducted at screening and study termination, and a urine/serum pregnancy test must be conducted at baseline; the results must be negative at screening and at baseline. WOCP must be advised to use acceptable contraceptives throughout the study period and for 30 days after the last dose of investigational product. If hormonal contraceptives are used they should be taken according to the package insert. WOCP who are not currently sexually active must agree to use acceptable contraception, as defined above, if they decide to become sexually active during the period of the study and for 30 days after the last dose of investigational product.
- Sexually active males whose partner is a WOCP must agree to use condoms for the duration of the study and for 30 days after the last dose;
- Women who are pregnant or breast feeding;
- Known or suspected hypersensitivity to the study medication or any of its ingredients;
- Have active atrial fibrillation (within the last 6 months) or, in the investigator's opinion, have any other significant cardiac arrhythmia;
- Any other significant systemic, hepatic or cardiac illness;
- Have a history of closed angle glaucoma;
- Have a known or suspected malignancy (other than basal cell carcinoma);
- Patients with known gastrointestinal illness or other gastrointestinal disorder that may, in the investigator's opinion, affect the absorption of study drug;
- In the investigator's opinion, have clinically significant abnormalities on clinical examination or laboratory testing;
- In the investigator's opinion, are unable to adequately cooperate because of individual or family situation;
- In the investigator's opinion, are suffering from a mental disorder that interferes with the diagnosis and/or with the conduct of the study, e.g. schizophrenia, major depression, dementia;
- Are not able or willing to comply with the study requirements for the duration of the study;
- Have participated in another clinical trial with an investigational agent (including named patient or compassionate use protocol) within 30 days before the start of the study;
- Previous enrollment in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II, Multi-center, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Assess the Clinical Benefit and Safety of Droxidopa in Patients With Intradialytic Hypotension
In clinical trials in Japan, droxidopa has been shown to be effective in affecting blood pressure changes upon orthostatic challenge in patients with autonomic dysfunction, as well as reducing the severity and frequency of symptoms of orthostatic hypotension in these patients. The efficacy of droxidopa in ameliorating symptoms in patients undergoing dialysis has also been demonstrated in the literature and clinical trials conducted in Japan. The current study will investigate the clinical efficacy of two different doses of droxidopa in patients with intradialytic hypotension over a 4 week treatment period with a placebo control. The clinical efficacy will be evaluated by changes in hypotension- related symptoms, as well as changes in blood pressure prior to, during and following, HD sessions as compared to their pre-treatment baseline values.
Read the detailed description
This is a phase II, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of droxidopa in HD patients with intradialytic hypotension. The study will be conducted in up to 15 centers, with a sufficient number of patients enrolled to allow 75 patients to be randomized into 3 study groups (25 randomized to placebo, 25 randomized to 400 mg droxidopa, and 25 randomized to 600 mg droxidopa).
The study will consist of an initial screening period (up to 7 days) to confirm eligibility followed by a 2 week baseline, and a 4 week treatment period. During baseline and treatment visits SBP and DBP measurements will be collected using a consistent method immediately pre-, during and immediately post-dialysis. SBP, DBP and heart rate measurements will be taken every 20 minutes during HD sessions.
There will be 19 scheduled visits, not including the post-treatment follow-up visit, during this trial; Visit 1 (Screening), Visits 2 through 7 (baseline and randomization), Visits 8 through 19 (tri-weekly treatment visits). Each visit will coincide with the patient's normal dialysis treatments.
All patients will be followed for 30 days following the completion of the active treatment period (or premature withdrawal) to check for the occurrence of adverse events (AEs).
Patients will attend the study center as out-patients.
Eligible patients will be assigned a unique identification number at screening, and prior to the first treatment visit will be randomized to one of the following treatment groups:
Group A: Droxidopa at 400 mg (2 capsules each containing 200 mg droxidopa plus one capsule with mannitol substituted for droxidopa) Group B: Droxidopa at 600 mg (3 capsules each containing 200 mg droxidopa) Group C: Placebo (3 capsules with mannitol substituted for droxidopa) Each patient will take 3 capsules 1 hour prior to each dialysis procedure with approximately 100 mL (typically half a glass) of water.
The primary measure of efficacy will be the change from baseline (visits 2-7) in average mean arterial blood pressure compared to that during treatment (visit 14-19).
The secondary measures of efficacy will be:
- Change between baseline (visits 2-7) and treatment (visits 14-19) in average mean nadir systolic and diastolic blood pressures during hemodialysis;
- Change in the number of hypotension-induced interventions during hemodialysis (HD) sessions;
- Change in hypotension-induced symptoms measured during hemodialysis;
- Change in daily symptoms associated with hemodialysis;
- Change in fatigue using the Multidimensional Fatigue Inventory (MFI-20). The safety of droxidopa will be evaluated based on the occurrence of treatment-emergent adverse events (AE) and specific evaluation of blood pressure, heart rate (HR), ECG, and laboratory findings across the study.
- Conditions
- Intradialytic Hypotension
- Being tested
- Droxidopa, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DroxidopaDrug
Capsules containing 200 mg droxidopa
PlaceboDrug
Capsules with mannitol substituted for droxidopa
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Droxidopa at 400 mg (2 capsules each containing 200 mg droxidopa plus one capsule with Placebo) Receives: Drug: Droxidopa; Drug: Placebo |
| 2 | Active comparator | Droxidopa at 600 mg (3 capsules each containing 200 mg droxidopa) Receives: Drug: Droxidopa |
| 3 | Placebo comparator | Placebo (3 capsules with mannitol substituted for droxidopa) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Average Mean Arterial Blood Pressure During Hemodialysis
Change between average baseline (visits 2-7) mean arterial blood pressure during hemodialysis and average treatment (visits 14-19) mean arterial blood pressure during hemodialysis.
The calculation of MAP was based on the systolic (SBP) and diastolic (DBP) blood pressure measurements taken during each valid HD session, using the traditional formula:
MAP = (SBP+2*DBP)/3 for each time-point. The mean of the intradialytic measurements was calculated for each valid HD session, and these daily mean values were averaged across the visits within each period.
Measured: 6 weeks
Secondary outcomes (5)
Change in Average Mean Nadir Systolic Blood Pressures During Hemodialysis;
Change between baseline (visits 2-7) and treatment (visits 14-19) in average mean nadir systolic blood pressures during hemodialysis. The baseline value will be the arithmetic average of the values collected at each of the six baseline visits (visits 2-7). The on treatment value will be defined as the average of the values collected at each of the last six treatment visits (visits 14-19).
Measured: 6 weeks
Change in the Number of Hypotension-induced Interventions During Hemodialysis (HD) Sessions;
Evaluate the efficacy of droxidopa as measured by change in the number of hypotension-induced interventions during hemodialysis (HD) sessions between baseline (visits 2-7) and treatment (visits 14-19). The baseline value will be the arithmetic average of the values collected at each of the six baseline visits (visits 2-7). The on treatment value will be defined as the average of the values collected at each of the last six treatment visits (visits 14-19).
Measured: 6 weeks
Change in the Hypotension-induced Symptom Severity Score
The hypotension-induced symptom severity score is the sum of a 6 question scale (each rated 0 [asymptomatic] to 4 [severe]). The questions look at cramps, dizziness, headache, nausea, itchiness, and restless legs syndrome experienced during dialysis.
The outcome looks at the difference between the average baseline score (visits 2-7) and the average on-treatment scores (visits 14-19). The baseline value will be the arithmetic average of the values collected at each of the six baseline visits (visits 2-7). The on treatment value will be defined as the average of the values collected at each of the last six treatment visits (visits 14-19).
Measured: 6 weeks
Daily Symptoms Associated With Hemodialysis
The Daily symptoms associated with hemodialysis score is the sum of an 8 question scale (each rated 0 [asymptomatic] to 4 [severe]). The questions look at fatigability, malaise/weakness, physical disturbance on standing, coldness of limbs, dizziness/lightheadedness, dizziness on standing, general bad feeling, and sleep disorders and asks how each of these items affected the patients daily activities on that day.
The outcome looks at the difference between the average baseline score (visits 2-7) and the average on-treatment scores (visits 14-19). The baseline value will be the arithmetic average of the values collected at each of the six baseline visits (visits 2-7). The on treatment value will be defined as the average of the values collected at each of the last six treatment visits (visits 14-19).
Measured: 6 weeks
Change in the Multidimensional Fatigue Inventory (MFI-20)
Fatigue will be measured by the general fatigue domain (items 1, 5, 12 and 16) of MFI-20 and will be summarized by treatment group and treatment period. The scores per item run from 1 to 5. A higher score indicates more fatigue. Therefore, the items indicative for fatigue need to be recoded (1=5, 2=4, 3=3, 4=2, 5=1). This concerns item: 5 and 16. A total score is calculated by summation of the scores of the individual items. Scores can range from the minimum of 4 to the maximum of 20.
The value at baseline (visit 7) will be subtracted from the value on treatment (visit 19 or visit 13 if visit 19 is not available).
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2008 (estimated)
- Study startDec 2007
- Primary completionJan 2009
- Study completionJan 2009
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.
- Other trials for Intradialytic HypotensionStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chelsea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rekha Halligan, MD, Principal investigator, Bayview Nephrology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00657046
- Sponsor's protocol ID
- Droxidopa IDH201
- Acronym
- IDH201
- Status last verified
- May 2014
- First submitted
- 8 Apr 2008
- Last updated
- 27 Jun 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Multi-center, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Assess the Clinical Benefit and Safety of Droxidopa in Patients With Intradialytic Hypotension
- ClinicalTrials.gov ID
- NCT00657046
- Acronym / sponsor ID
- IDH201 / Droxidopa IDH201
- Conditions
- Intradialytic Hypotension
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Chelsea TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Dec 2007
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 14 Apr 2008 (estimated)
- Results
- Posted 27 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In clinical trials in Japan, droxidopa has been shown to be effective in affecting blood pressure changes upon orthostatic challenge in patients with autonomic dysfunction, as well as reducing the severity and frequency of symptoms of orthostatic hypotension in these patients. The efficacy of droxidopa in ameliorating symptoms in patients undergoing dialysis has also been demonstrated in the literature and clinical trials conducted in Japan. The current study will investigate the clinical efficacy of two different doses of droxidopa in patients with intradialytic hypotension over a 4 week treatment period with a placebo control. The clinical efficacy will be evaluated by changes in hypotension- related symptoms, as well as changes in blood pressure prior to, during and following, HD sessions as compared to their pre-treatment baseline values.
Detailed description
This is a phase II, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of droxidopa in HD patients with intradialytic hypotension. The study will be conducted in up to 15 centers, with a sufficient number of patients enrolled to allow 75 patients to be randomized into 3 study groups (25 randomized to placebo, 25 randomized to 400 mg droxidopa, and 25 randomized to 600 mg droxidopa).
The study will consist of an initial screening period (up to 7 days) to confirm eligibility followed by a 2 week baseline, and a 4 week treatment period. During baseline and treatment visits SBP and DBP measurements will be collected using a consistent method immediately pre-, during and immediately post-dialysis. SBP, DBP and heart rate measurements will be taken every 20 minutes during HD sessions.
There will be 19 scheduled visits, not including the post-treatment follow-up visit, during this trial; Visit 1 (Screening), Visits 2 through 7 (baseline and randomization), Visits 8 through 19 (tri-weekly treatment visits). Each visit will coincide with the patient's normal dialysis treatments.
All patients will be followed for 30 days following the completion of the active treatment period (or premature withdrawal) to check for the occurrence of adverse events (AEs).
Patients will attend the study center as out-patients.
Eligible patients will be assigned a unique identification number at screening, and prior to the first treatment visit will be randomized to one of the following treatment groups:
Group A: Droxidopa at 400 mg (2 capsules each containing 200 mg droxidopa plus one capsule with mannitol substituted for droxidopa) Group B: Droxidopa at 600 mg (3 capsules each containing 200 mg droxidopa) Group C: Placebo (3 capsules with mannitol substituted for droxidopa) Each patient will take 3 capsules 1 hour prior to each dialysis procedure with approximately 100 mL (typically half a glass) of water.
The primary measure of efficacy will be the change from baseline (visits 2-7) in average mean arterial blood pressure compared to that during treatment (visit 14-19).
The secondary measures of efficacy will be:
- Change between baseline (visits 2-7) and treatment (visits 14-19) in average mean nadir systolic and diastolic blood pressures during hemodialysis;
- Change in the number of hypotension-induced interventions during hemodialysis (HD) sessions;
- Change in hypotension-induced symptoms measured during hemodialysis;
- Change in daily symptoms associated with hemodialysis;
- Change in fatigue using the Multidimensional Fatigue Inventory (MFI-20). The safety of droxidopa will be evaluated based on the occurrence of treatment-emergent adverse events (AE) and specific evaluation of blood pressure, heart rate (HR), ECG, and laboratory findings across the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Droxidopa, Drug: PlaceboDroxidopa at 400 mg (2 capsules each containing 200 mg droxidopa plus one capsule with Placebo) |
| 2 | Active comparator | Drug: DroxidopaDroxidopa at 600 mg (3 capsules each containing 200 mg droxidopa) |
| 3 | Placebo comparator | Drug: PlaceboPlacebo (3 capsules with mannitol substituted for droxidopa) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female and aged 18 years or over;
- Clinical diagnosis of ESRD;
- Demonstrated requirement to undergo maintenance HD 3 times per week for sessions at least 3 hours in duration;
- Medical history consistent with IDH existing for at least 1 month;
- Observed symptomatic intradialytic hypotension in 3 of 6 HD sessions during screening, as defined by as a decrease in systolic blood pressure by ≥20 mm Hg or a decrease in MAP by 10 mm Hg associated with symptoms that include: abdominal discomfort; yawning; sighing; nausea; vomiting; muscle cramps; restlessness; dizziness or fainting; and anxiety (definition according to: National Kidney Foundation 2007) ;
Key exclusion criteria (23 listed)
- Currently taking ephedrine or midodrine;
- Taking anti-hypertensive medication on the day of dialysis;
- Currently taking selective norepinephrine re-uptake inhibitors;
- Current known or suspected drug or substance abuse;
- Women of childbearing potential who are not using a medically accepted contraception;
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 |
|---|---|---|
| DroxidopaCapsules containing 200 mg droxidopa | Drug | 1, 2 |
| PlaceboCapsules with mannitol substituted for droxidopa | Drug | 1, 3 |
Primary outcome
Change in Average Mean Arterial Blood Pressure During Hemodialysis
Time frame: 6 weeks
Change between average baseline (visits 2-7) mean arterial blood pressure during hemodialysis and average treatment (visits 14-19) mean arterial blood pressure during hemodialysis. The calculation of MAP was based on the systolic (SBP) and diastolic (DBP) blood pressure measurements taken during each valid HD session, using the traditional formula: MAP = (SBP+2*DBP)/3 for each time-point. The mean of the intradialytic measurements was calculated for each valid HD session, and these daily mean values were averaged across the visits within each period.
5 secondary outcomes
Change in Average Mean Nadir Systolic Blood Pressures During Hemodialysis;
Time frame: 6 weeks
Change in the Number of Hypotension-induced Interventions During Hemodialysis (HD) Sessions;
Time frame: 6 weeks
Change in the Hypotension-induced Symptom Severity Score
Time frame: 6 weeks
Daily Symptoms Associated With Hemodialysis
Time frame: 6 weeks
Change in the Multidimensional Fatigue Inventory (MFI-20)
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Rekha Halligan, MD principal investigator
Bayview Nephrology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Droxidopa in people with Intradialytic Hypotension, run by Chelsea Therapeutics at 1 site in United States.
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 6 inclusion and 23 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 27 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 27 Jun 2014). 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?
Change in Average Mean Arterial Blood Pressure During Hemodialysis (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jun 2014.