Purpura, Thrombotic ThrombocytopenicEarly Phase 1NACinTTPNCT01808521
A Pilot Study of N-acetylcysteine in Thrombotic Thrombocytopenia Purpura
A Early Phase 1 study testing N-Acetylcysteine in people with Purpura, Thrombotic Thrombocytopenic and TTP, run by Bloodworks at 1 site in United States.
Trial summary
In this study, the investigators want to determine if N-acetylcysteine(NAC), given intravenously, will decrease complications in patients with Thrombotic Thrombocytopenia Purpura (TTP) who are receiving treatment with therapeutic plasma exchange (TPE). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Purpura, Thrombotic Thrombocytopenic, TTP
- What is being tested?
- N-Acetylcysteine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- May 2013to Jul 2017
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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
- Age >= 18 years of age
- Diagnosis of suspected TTP (lab evidence of hemolysis, platelet count <120,000, schistocytes on peripheral smear)
- Plans for or just initiated therapeutic plasma exchange (TPE), and before 3rd TPE
- Normal baseline prothrombin time (PT) and activated partial thromboplastin time (aPTT)
- Anticipated TPE for > 5 days
Who cannot join
- Asthma
- Life expectancy < 1 week
- Liver function tests abnormal- (ALT, direct bilirubin > three times upper normal limit)
- Known underlying bleeding disorder
- Pregnancy or nursing
- Known allergy to NAC
- Phosphodiesterase Type 5 inhibitors, nitroglycerin, or carbamazepine current use
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study of N-acetylcysteine in Suspected Thrombotic Thrombocytopenia Purpura
In this study, the investigators want to determine if N-acetylcysteine(NAC), given intravenously, will decrease complications in patients with Thrombotic Thrombocytopenia Purpura (TTP) who are receiving treatment with therapeutic plasma exchange (TPE). The investigators want to determine, through anti-oxidant activity, if NAC will have additional efficacy in TTP by improving cleavage of the patients' VWF by ADAMTS13, and preventing propagation of platelet/VWF strings. This will be manifest by a more rapid improvement in the patient's platelet count, decrease in number of days requiring TPE, and decrease in microvascular thrombotic complications. The investigators will additionally: 1) Assess safety of NAC by evaluating subjects for adverse events and significant adverse events 2) Determine effects on TTP by measuring clinical and research laboratory values 3) Determine drug effects by measuring clinical and research laboratory values.
Read the detailed description
Thrombotic thrombocytopenic purpura (TTP) is a rare hemostatic disorder with life threatening consequences secondary to microvascular thrombosis. While the use of therapeutic plasma exchange (TPE) has greatly improved survival, end organ damage, resistance to therapy, and relapses occur in many patients. Ultra-large von Willebrand factor multimers (ULVWF) are pathogenic in TTP. The investigators have found that N-acetylcysteine (NAC) cleaves ULVWF in vitro and in vivo in the ADAMTS13 deficient mice that are at increased risk of TTP. NAC is well tolerated in humans at intravenous doses used for treatment of acetaminophen overdose. This dosage correlates with that producing an effect in the murine studies noted above, and thus is an attractive treatment for patients with TTP. By cleaving VWF and preventing propagation of platelet/VWF strings, the investigators hypothesize that NAC treatment will decrease complications in patients with TTP receiving treatment with TPE. This will be manifest by a more rapid improvement in platelet count, decrease in number of days requiring plasma exchange, and decrease in microvascular thrombotic complications. To prepare for a larger trial the investigators propose a pilot study in 3 patients with suspected TTP at the University of Washington (UW) Medical Center. The study will be approved by the UW IRB prior to study initiation. Patients who consent to the study will receive daily NAC infusions beginning after the first TPE, in doses used for acetaminophen overdose. Blood samples will be collected for laboratory assays to determine optimal timing for sample collection in the larger multicenter trial, and to pilot the data collection forms. The investigators will also evaluate safety and patient tolerability.
- Conditions
- Purpura, Thrombotic Thrombocytopenic, TTP
- Being tested
- N-Acetylcysteine
- Keywords
- Purpura, Thrombotic Thrombocytopenic, TTP
- Medical subject headings
- Purpura, Thrombotic Thrombocytopenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-AcetylcysteineDrug
Also called Acetadote
IV administration of N-Acetylcysteine at 150mg/kg over 60 min first, then if well tolerated, 150mb/kg over 17 hours
| Study group | Role | What they receive |
|---|---|---|
| N-acetylcysteine | Experimental | IV administration of N-acetylcysteine (Acetadote) at 150mg/Kg loading bolus over 60 minutes followed by 150mg/Kg over 17 hours if loading dose was well tolerated. Receives: Drug: N-Acetylcysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in platelet count
The platelet count will be measured before, daily during 4 days of NAC infusion, the subsequent 3 days and on the day of hospital discharge which is estimated to be at 1-2 weeks post infusion. Changes in platelet count over time will be reported.
Measured: Daily for 7 days and at hospital discharge, expected to be at 1-2 weeks post infusion.
Secondary outcomes (4)
Laboratory measures of VWF activity
VWF levels, oxidation and activity will be measured before, each day of NAC infusion, the subsequent 3 days and at hospital discharge, expected to be at 1-2 weeks post-infusion. Changes in values over time will be reported.
Measured: Daily for 7 days and at hospital dischargewhich is estimated to be at 1-2 weeks post-infusion
Laboratory measures of ADAMTS13 activity
ADAMTS13 level, oxidation and activity will be measured before, daily during the NAC infusion, for the 3 subsequent days and at hospital discharge, expected to be at 1-2 weeks post-infusion. Changes over time will be reported.
Measured: Daily for 7 days and at hospital discharge which is estimated to be at 1-2 weeks post-infusion
Laboratory measures of red blood cell (RBC) hemolysis and oxidation
Laboratory markers of RBC hemolysis and oxidation will be measured before, daily during the NAC infusion, for 3 subsequent days and at hospital discharge, expected to be at 1-2 weeks post-infusion. Changes in values over time will be reported.
Measured: Daily for 7 days and at hospital discharge which is estimated to be at 1-2 weeks post-infusion
Safety of NAC infusion
Adverse events will be collected daily during the hospitalization, at 2 weeks and 8 weeks following infusion.
Measured: Over the study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2013 (estimated)
- Study startMay 2013
- Primary completionJul 2017
- Study completionJul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Purpura, Thrombotic ThrombocytopenicStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bloodworks
- Sponsor type
- University, hospital or other
- Collaborators
- University of Washington
- Responsible party
- Sponsor
- Investigators
- Barbara A Konkle, MD, Principal investigator, Bloodworks
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01808521
- Sponsor's protocol ID
- N-Acetylcysteine in TTP
- Acronym
- NACinTTP
- Status last verified
- Sep 2017
- First submitted
- 22 Feb 2013
- Last updated
- 20 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of N-acetylcysteine in Suspected Thrombotic Thrombocytopenia Purpura
- ClinicalTrials.gov ID
- NCT01808521
- Acronym / sponsor ID
- NACinTTP / N-Acetylcysteine in TTP
- Conditions
- Purpura, Thrombotic Thrombocytopenic, TTP
- Keywords
- Purpura, Thrombotic Thrombocytopenic, TTP
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- BloodworksUniversity, hospital or other
- Collaborators
- University of Washington
- Study start
- May 2013
- Primary completion
- Jul 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 11 Mar 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, the investigators want to determine if N-acetylcysteine(NAC), given intravenously, will decrease complications in patients with Thrombotic Thrombocytopenia Purpura (TTP) who are receiving treatment with therapeutic plasma exchange (TPE). The investigators want to determine, through anti-oxidant activity, if NAC will have additional efficacy in TTP by improving cleavage of the patients' VWF by ADAMTS13, and preventing propagation of platelet/VWF strings. This will be manifest by a more rapid improvement in the patient's platelet count, decrease in number of days requiring TPE, and decrease in microvascular thrombotic complications. The investigators will additionally: 1) Assess safety of NAC by evaluating subjects for adverse events and significant adverse events 2) Determine effects on TTP by measuring clinical and research laboratory values 3) Determine drug effects by measuring clinical and research laboratory values.
Detailed description
Thrombotic thrombocytopenic purpura (TTP) is a rare hemostatic disorder with life threatening consequences secondary to microvascular thrombosis. While the use of therapeutic plasma exchange (TPE) has greatly improved survival, end organ damage, resistance to therapy, and relapses occur in many patients. Ultra-large von Willebrand factor multimers (ULVWF) are pathogenic in TTP. The investigators have found that N-acetylcysteine (NAC) cleaves ULVWF in vitro and in vivo in the ADAMTS13 deficient mice that are at increased risk of TTP. NAC is well tolerated in humans at intravenous doses used for treatment of acetaminophen overdose. This dosage correlates with that producing an effect in the murine studies noted above, and thus is an attractive treatment for patients with TTP. By cleaving VWF and preventing propagation of platelet/VWF strings, the investigators hypothesize that NAC treatment will decrease complications in patients with TTP receiving treatment with TPE. This will be manifest by a more rapid improvement in platelet count, decrease in number of days requiring plasma exchange, and decrease in microvascular thrombotic complications. To prepare for a larger trial the investigators propose a pilot study in 3 patients with suspected TTP at the University of Washington (UW) Medical Center. The study will be approved by the UW IRB prior to study initiation. Patients who consent to the study will receive daily NAC infusions beginning after the first TPE, in doses used for acetaminophen overdose. Blood samples will be collected for laboratory assays to determine optimal timing for sample collection in the larger multicenter trial, and to pilot the data collection forms. The investigators will also evaluate safety and patient tolerability.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| N-acetylcysteine | Experimental | Drug: N-AcetylcysteineIV administration of N-acetylcysteine (Acetadote) at 150mg/Kg loading bolus over 60 minutes followed by 150mg/Kg over 17 hours if loading dose was well tolerated. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age >= 18 years of age
- Diagnosis of suspected TTP (lab evidence of hemolysis, platelet count <120,000, schistocytes on peripheral smear)
- Plans for or just initiated therapeutic plasma exchange (TPE), and before 3rd TPE
- Normal baseline prothrombin time (PT) and activated partial thromboplastin time (aPTT)
- Anticipated TPE for > 5 days
Key exclusion criteria (7 listed)
- Asthma
- Life expectancy < 1 week
- Liver function tests abnormal- (ALT, direct bilirubin > three times upper normal limit)
- Known underlying bleeding disorder
- Pregnancy or nursing
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 |
|---|---|---|
| N-AcetylcysteineAlso: AcetadoteIV administration of N-Acetylcysteine at 150mg/kg over 60 min first, then if well tolerated, 150mb/kg over 17 hours | Drug | N-acetylcysteine |
Primary outcome
Changes in platelet count
Time frame: Daily for 7 days and at hospital discharge, expected to be at 1-2 weeks post infusion.
The platelet count will be measured before, daily during 4 days of NAC infusion, the subsequent 3 days and on the day of hospital discharge which is estimated to be at 1-2 weeks post infusion. Changes in platelet count over time will be reported.
4 secondary outcomes
Laboratory measures of VWF activity
Time frame: Daily for 7 days and at hospital dischargewhich is estimated to be at 1-2 weeks post-infusion
Laboratory measures of ADAMTS13 activity
Time frame: Daily for 7 days and at hospital discharge which is estimated to be at 1-2 weeks post-infusion
Laboratory measures of red blood cell (RBC) hemolysis and oxidation
Time frame: Daily for 7 days and at hospital discharge which is estimated to be at 1-2 weeks post-infusion
Safety of NAC infusion
Time frame: Over the study period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2017.
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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.
Barbara A Konkle, MD principal investigator
Bloodworks
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing N-Acetylcysteine in people with Purpura, Thrombotic Thrombocytopenic and TTP, run by Bloodworks 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 5 inclusion and 7 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 20 Sep 2017. 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Changes in platelet count (time frame: Daily for 7 days and at hospital discharge, expected to be at 1-2 weeks post infusion.). 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 20 Sep 2017.