Efficacy and Safety of Apixaban in the Treatment of Heparin Induced Thrombocytopenia (HIT)

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03594045
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 5
• Locations: 3
• Arms: 2
• Actual Duration (Months): 10.4
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This research study is studying a drug as a possible treatment for heparin induced thrombocytopenia (HIT) or Heparin-induced Thrombocytopenia and Thrombosis (HITT).

The drug involved in this study is apixaban.

Condition or Disease	Intervention/Treatment	Phase
Heparin-induced Thrombocytopenia; Heparin-induced Thrombocytopenia and Thrombosis	Drug: Apixaban	Phase 2

Detailed Description

This research study is a Phase II clinical trial.

The FDA (the U.S. Food and Drug Administration) has not approved apixaban as a treatment option for this specific disease but it has been approved for other uses.

HIT and HITT are common and severe complications of heparin therapy. Once patients are diagnosed with either one of these, they are typically switched to a non-heparin anticoagulant (a type of drug that thins your blood). As of now the only drug that is FDA approved for HIT or HITT is argatroban, which is administered continuously through an IV over multiple days and is extremely costly.

In this research study, the investigators are researching the activity and tolerability of apixaban in participants with HIT or HITT. The investigators believe that apixaban will work just as well as argatroban and will be more convenient for this population. The oral route of apixaban allows for the potential outpatient treatment of HIT or HITT which is both convenient and less expensive than treatment with argatroban.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study to Evaluate the Efficacy and Safety of Apixaban in the Treatment of Heparin Induced Thrombocytopenia (HIT)
• Actual Study Start Date: Dec 18, 2018
• Actual Primary Completion Date: Oct 30, 2019
• Actual Study Completion Date: Oct 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apixaban for HIT Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days.	Drug: Apixaban; Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.
Experimental: Apixaban for HITT Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months.	Drug: Apixaban; Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.

Outcome Measures

Primary Outcome Measures

1. Cumulative Incidence of New Symptomatic Thromboembolic Complications (TEC) Within 30 Days of the Initiation of Apixaban [30 days]

   New TEC

Secondary Outcome Measures

1. Composite Cumulative Incidence of All-cause Mortality, Limb Amputation and New TEC [From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT]

   Composite cumulative incidence

2. Composite Cumulative Incidence of New TEC and Major Bleeding [From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT]

   Composite cumulative incidence

3. Cumulative Incidence of Major Bleeding [From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT]

   Major Bleeding

4. Time to Platelet Recovery [From the start of treatment until time of platelet recovery, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT]

   The time to platelet recovery serves as a surrogate index of the activity of apixaban.

5. Cumulative Incidence of All Cause Mortality [From the start of treatment until the time of death or until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT]

   Death due to any cause during treatment or the follow-up period following treatment.

6. Cumulative Incidence of Limb Amputation [From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT]

7. Cumulative Incidence of New Thromboembolic Complications (TEC) [From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT]

   New TEC during the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Hospitalized patients at MGH and participating Dana Farber/Harvard Cancer Center (DF/HCC) sites.

• Patient must have a diagnosis of HIT or high clinical suspicion of HIT, with a 4 T score of ≥ 5 as calculated by the following criteria:

• Thrombocytopenia

• Platelet count fall >50 percent and nadir ≥20,000/microL - 2 points

• Platelet count fall 30 to 50 percent or nadir 10 to 19,000/microL - 1 points

• Platelet count fall <30 percent or nadir <10,000/microL - 0 points

• Timing of platelet count fall

• Clear onset between days 5 and 10 or platelet count fall at ≤1 day if prior heparin exposure within the last 30 days - 2 points

• Consistent with fall at 5 to 10 days but unclear (eg, missing platelet counts), onset after day 10, or fall ≤1 day with prior heparin exposure within 30 to 100 days - 1 point

• Platelet count fall at <4 days without recent exposure - 0 points

• Thrombosis or other sequelae

• Confirmed new thrombosis, skin necrosis, or acute systemic reaction after intravenous unfractionated heparin bolus - 2 points

• Progressive or recurrent thrombosis, non-necrotizing (erythematous) skin lesions, or suspected thrombosis that has not been proven - 1 point

• None - 0 points

• Other causes for thrombocytopenia

• None apparent - 2 points

• Possible - 1 point

• Definite - 0 points

• Prior to or immediately subsequent to enrollment, the patient must have the diagnosis confirmed by Heparin-PF4 EIA or other accepted confirmatory test to remain on study.

• Patients can be treated with argatroban, bivalirudin or fondaparinux for up to 72 hours prior to enrollment.

• Age 18 years or older.

• ECOG performance status ≤2 (Karnofsky ≥60%)

• Participants must have organ and marrow function as defined below:

• absolute neutrophil count ≥1,500/mcL

• AST(SGOT) and ALT(SGPT) ≤2.5 × institutional upper limit of normal

• creatinine clearance ≥25 mL/min as was used in the AMPLIFY trial16

• The effects of apixaban on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study entry, for the duration of the study participation, and 4 months after completion of apixaban administration.

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patient requires anticoagulation for a mechanical heart valve.

• Patient requires:

• anticoagulation for another indication for long-term anticoagulation therapy,

• dual antiplatelet therapy,

• treatment with aspirin at a dose of more than 162 mg daily

• Patient has signs of active or ongoing clinically significant hemorrhage.

• Patient has hereditary or acquired coagulopathy or bleeding disorder.

• Patient has a contraindication to apixaban.

• Participants receiving any medications or substances that are inhibitors or inducers of cytochrome P-450 3A4 or p-glycoprotein are ineligible. Because this list of these agents are constantly changing, it is important to regularly consult a frequently-updated list. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.

• Patient has severe renal insufficiency (CrCl <25 ml/min-as used in the AMPLIFY trial)

• Patient has hepatic disease (including Child-Pugh B and C) associated with coagulopathy or clinically relevant bleeding risk.

• Recent (previous seven days), or complicated lumbar puncture or epidural catheter placement or removal.

• Patient has high potential need to undergo a surgical or major invasive procedure in the near future.

• Patient has a history of uncorrected cerebral aneurysm, intracranial tumor or hemorrhagic cerebrovascular accident.

• Patient refuses to receive transfused blood products should this intervention become clinically indicated.

• Patient is taking or has been taking an investigational drug within the previous 30 days prior to enrollment.

• In the judgment of the investigator, any disease or circumstance that would interfere with the objectives of the study.

• Participants with known brain metastases.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to apixaban.

• Uncontrolled intercurrent illness.

• Pregnant women are excluded; breastfeeding should be discontinued if the mother is treated with apixaban.

• Prior treatment with a non-heparin anticoagulant while awaiting study enrollment is not an exclusion.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02214
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
3	Brigham and Women Hospital	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Massachusetts General Hospital
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Rachel P Rosovsky, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 16, 2019

More Information

Publications

None provided.

• Responsible Party: Rachel P. Rosovsky, MD, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03594045
• Other Study ID Numbers: 18-153
• First Posted: Jul 20, 2018
• Last Update Posted: Dec 23, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Rachel P. Rosovsky, MD, Principal Investigator, Massachusetts General Hospital: Heparin-induced Thrombocytopenia
• Additional relevant MeSH terms: Thrombosis; Thrombocytopenia; Apixaban

Study Results

Participant Flow

Arm/Group Title	Apixaban for HIT	Apixaban for HITT
Arm/Group Description	Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.	Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.
Period Title: Overall Study
STARTED	0	5
COMPLETED	0	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Apixaban for HIT	Apixaban for HITT	Total
Arm/Group Description	Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.	Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.	Total of all reporting groups
Overall Participants	0	5	5
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	68	68
Sex: Female, Male (Count of Participants)
Female	2 Infinity	2 40%
Male	3 Infinity	3 60%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 NaN
Region of Enrollment (participants) [Number]
United States	5 Infinity	5 100%

Outcome Measures

1. Primary Outcome

Title	Cumulative Incidence of New Symptomatic Thromboembolic Complications (TEC) Within 30 Days of the Initiation of Apixaban
Description	New TEC
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

No HIT patients were enrolled

Arm/Group Title	Apixaban for HIT	Apixaban for HITT
Arm/Group Description	Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.	Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.
Measure Participants	0	5
Count of Participants [Participants]	0 NaN

2. Secondary Outcome

Title	Composite Cumulative Incidence of All-cause Mortality, Limb Amputation and New TEC
Description	Composite cumulative incidence
Time Frame	From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT

Outcome Measure Data

Analysis Population Description

No HIT patients were enrolled

Arm/Group Title	Apixaban for HIT	Apixaban for HITT
Arm/Group Description	Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.	Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.
Measure Participants	0	5
Count of Participants [Participants]	0 NaN

3. Secondary Outcome

Title	Composite Cumulative Incidence of New TEC and Major Bleeding
Description	Composite cumulative incidence
Time Frame	From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT

Outcome Measure Data

Analysis Population Description

No HIT patients were enrolled

Arm/Group Title	Apixaban for HIT	Apixaban for HITT
Arm/Group Description	Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.	Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.
Measure Participants	0	5
Count of Participants [Participants]	0 NaN

4. Secondary Outcome

Title	Cumulative Incidence of Major Bleeding
Description	Major Bleeding
Time Frame	From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT

Outcome Measure Data

Analysis Population Description

No HIT patients were enrolled

Arm/Group Title	Apixaban for HIT	Apixaban for HITT
Arm/Group Description	Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.	Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.
Measure Participants	0	5
Count of Participants [Participants]	0 NaN

5. Secondary Outcome

Title	Time to Platelet Recovery
Description	The time to platelet recovery serves as a surrogate index of the activity of apixaban.
Time Frame	From the start of treatment until time of platelet recovery, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT

Outcome Measure Data

Analysis Population Description

No HIT patients were enrolled

Arm/Group Title	Apixaban for HIT	Apixaban for HITT
Arm/Group Description	Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.	Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.
Measure Participants	0	5
Median (Full Range) [Days]	2

6. Secondary Outcome

Title	Cumulative Incidence of All Cause Mortality
Description	Death due to any cause during treatment or the follow-up period following treatment.
Time Frame	From the start of treatment until the time of death or until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT

Outcome Measure Data

Analysis Population Description

No HIT patients were enrolled

Arm/Group Title	Apixaban for HIT	Apixaban for HITT
Arm/Group Description	Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.	Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.
Measure Participants	0	5
Count of Participants [Participants]	0 NaN

7. Secondary Outcome

Title	Cumulative Incidence of Limb Amputation
Time Frame	From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT

Outcome Measure Data

Analysis Population Description

No HIT patients were enrolled

Arm/Group Title	Apixaban for HIT	Apixaban for HITT
Arm/Group Description	Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.	Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.
Measure Participants	0	5
Count of Participants [Participants]	0 NaN

8. Secondary Outcome

Title	Cumulative Incidence of New Thromboembolic Complications (TEC)
Description	New TEC during the study.
Time Frame	From the start of treatment until 30 days after the end of treatment, up to 60 days total for participants with HIT and up to 120 days total for participants with HITT

Outcome Measure Data

Analysis Population Description

No HIT patients were enrolled

Arm/Group Title	Apixaban for HIT	Apixaban for HITT
Arm/Group Description	Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.	Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.
Measure Participants	0	5
Count of Participants [Participants]	0 NaN

Adverse Events

Time Frame	From the start of treatment until 3 days after the last treatment was received, up to approximately 4 months
Adverse Event Reporting Description	No HIT patients were enrolled
Arm/Group Title	Apixaban for HIT		Apixaban for HITT
Arm/Group Description	Patients with Heparin Induced Thrombocytopenia (HIT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 30 days. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.		Patients with Heparin Induced Thrombocytopenia with Thrombosis (HITT) will receive Apixaban, at an initial dose of 10 mg orally twice a day for 7 days followed by 5 mg twice a day for a total of 3 months. Apixaban: Apixaban is an anticoagulant that works by inhibiting the coagulation factor, Factor Xa.
All Cause Mortality
	Apixaban for HIT		Apixaban for HITT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/5 (0%)
Serious Adverse Events
	Apixaban for HIT		Apixaban for HITT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Apixaban for HIT		Apixaban for HITT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		4/5 (80%)
General disorders
Fatigue	0/0 (NaN)	0	1/5 (20%)	3
Fever	0/0 (NaN)	0	1/5 (20%)	3
Non-cardiac chest pain	0/0 (NaN)	0	2/5 (40%)	6
Pain	0/0 (NaN)	0	1/5 (20%)	2
Infections and infestations
Lung infection	0/0 (NaN)	0	1/5 (20%)	6
Sepsis	0/0 (NaN)	0	1/5 (20%)	3
Urinary tract infection	0/0 (NaN)	0	1/5 (20%)	6
Wound infection	0/0 (NaN)	0	1/5 (20%)	3
Injury, poisoning and procedural complications
Bruising	0/0 (NaN)	0	1/5 (20%)	3
Investigations
Weight loss	0/0 (NaN)	0	1/5 (20%)	3
Metabolism and nutrition disorders
Hypokalemia	0/0 (NaN)	0	1/5 (20%)	3
Nervous system disorders
Dizziness	0/0 (NaN)	0	1/5 (20%)	5
Tremor	0/0 (NaN)	0	1/5 (20%)	4
Psychiatric disorders
Insomnia	0/0 (NaN)	0	1/5 (20%)	4
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/0 (NaN)	0	1/5 (20%)	2
Epistaxis	0/0 (NaN)	0	1/5 (20%)	5
Respiratory failure	0/0 (NaN)	0	1/5 (20%)	3
Skin and subcutaneous tissue disorders
Dry skin	0/0 (NaN)	0	1/5 (20%)	2
Nail discoloration	0/0 (NaN)	0	1/5 (20%)	2
Vascular disorders
Hematoma	0/0 (NaN)	0	1/5 (20%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.