CONSORT Plus Trial Reporting Example

Here is an example of a randomized trial reported along the lines of the CONSORT Plus guidelines. For illustrative purposes, this example includes the reporting of most of the Recommended and Optional items as well as all the Required items. To see how you could browse this information selectively, go to RCT Presenter.

Administration

• Study Name: Stroke Prevention in Non-Rheumatic Atrial Fibrillation
• Official Abbreviation: SPINAF

Investigators

• Group Authorship Name: The SPINAF Investigators

Ethics

• Approved by Institutional Review Board(s)? Yes
• Comment: n.r.
• Informed consent? Yes
• Comment: Informed consent will be obtained by either the participating cardiologist, or the participating neurologist, or by another specifically designated physician in the event both of them are unavailable. Patients who consent to enter the study must sign both the information sheet and VA Form 10-1086. Specific items such as duration of the study, the testing necessary to enter, the frequency of follow-up visits, the need to forego aspirin therapy, and the voluntary nature of participation will be discussed prior to obtaining informed consent. Informed consent will be obtained at the completion of screening, prior to acquisition of entry history, physical and neurologic examination, and non-invasive imaging battery.

Contact Person

• Name: KE James PhD
• Comment: n.r.

Funding

Oversight Committees

• Executive Committee:

• CT Scan Committee:

Study Sites

• Total Study Sites: 16
• Total US Sites: 16
• Total Non-US Sites: 0
• Total sites withdrawn from participation: 3
• Total sites added to original protocol: 2

Original Sites

Late Addition Sites

Withdrawn Sites

Stage of Trial

• Trial is currently completed, fully reported.

Study Objectives

• Primary Objectives
  • 1. To determine if long-term low intensity oral anticoagulation will result in a significant reduction in stroke incidence in patients with nonvalvular atrial fibrillation and no history of prior stroke.
  • 2. To determine if atrial size, left ventricular dysfunction or the presence of prior subclinical cerebral infarction will predict greater stroke risk in nonvalvular atrial fibrillation, and to determine the efficacy of long-term low intensity anticoagulation in the presence of these risk factors.
• Secondary Objectives
  • 1. To determine the incidence and nature of hemorrhagic complications of long-term low intensity oral anticoagulation in patients with nonvalvular atrial fibrillation.
• Background
  • It is generally accepted that atrial fibrillation is associated with an increased risk of stroke. The risk among patients with non-rheumatic atrial fibrillation is estimated to be five times greater than that for comparable patients in sinus rhythm. It is also known that the prevalence of no-nrheumatic atrial fibrillation increases with age, with rates increasing from 0.04 percent per year among men under the age of 50 years to 9 percent per year among older men. Studies of low-intensity anticoagulation with warfarin, first used in the treatment of deep-vein thrombosis and more recently for other clinical conditions, have demonstrated that low-intensity anticoagulation is equal in efficacy to anticoagulation at a higher intensity in preventing thromboembolic episodes, but that it is associated with a lower risk of bleeding.

Power and Sample Size Calculations

Statistical Analysis

• Intention to treat analysis? Yes
• Fundamental Approach: Classical
• Alpha: 0.05, 2-tailed

• Handling of losses to follow-up: Follow-up censored at the time of last contact?, Patients withdrawn from study medication will receive regular follow-up until the end of the 3 year follow-up period or until the occurrence of an endpoint. Patients experiencing a cerebral endpoint will be monitored only for survival until the completion of the 3-year follow-up period.
• Click here to see the analysis methods for particular outcomes.

Hypotheses

Subgroup Definitions

A priori

These clinical subgroups were defined before the start of trial enrollment.

Post-hoc

These clinical subgroups were defined after the start of trial enrollment

Study Monitoring

• Data Monitoring Board

• Definition of stopping rule: n.r.
• Schedule of rule application: Scheduled to be applied February of 1991 and again in February 1992.
• Interim analysis by: Data Monitoring Board
• Comments: Based on results of published studies and interim finding of 72% reduction in the rate of infarction among patients given warfarin, the board recommended termination of the study, which occurred on March 1, 1991., The first interim results were presented to the Data Monitoring Board on Jan 21, 1991 and were based on data obtained through December 1, 1990.

Protocol Changes

Why Study Stopped

• Study stopped: On the basis of published studies (AFASAK, BAATAF, and SPAF) and on our finding in the interim analysis of a 72 percent reduction in the rate of cerebral infarction among patients given warfarin, the board recommended termination of the study, which occurred on March 1, 1991.

Inclusion Criteria

Participants must satisfy the following criteria.

Exclusion Criteria

Participants must not satisfy any of the following criteria. Some participants were excluded for more than one reason.

Recruitment

Recruitment and Screening Method

• Patients were recruited from VA hospitals in an unstated manner. Patients excluded for non-permanent reasons were rescreened, again in an unspecified manner.

Source of Subjects

• Generally older male patients, all veterans of US Armed Forces, from throughout the US.
• Click here for information about the study sites.

Dates of Recruitment

• Start date: Jun 1, 1987
• End date: May 30, 1990
• Comments: A pilot survey was conducted in 1986 with 7 VA centers to estimate patient availability. Duration of recruitment and number of centers needed was based on this and other survey information.

Recruitment Flowchart

Randomization and Assignment

Evidence of Randomization Efficacy

Evidence of Blinding Efficacy

Interventions

Placebo

• Intervention type: Drug
• Activity of control: Placebo
• Similarity to experimental intervention: Placebo identical in appearance to the active medication, also manufactured by E.I. DuPont & Company.
• Justification for control: One of the important clinical issues remaining unresolved is: what should be done, if anything, to prevent stroke in patients with nonvalvular atrial fibrillation? Currently, any decision rests largely on opinion and personal experience, as no prospective data regarding this isuse are available.

• Delay between randomization and start of treatment: n.r.

Warfarin

• Intervention type: Drug
• Generic name: Sodium warfarin
• Trade name: Coumadin
• Manufacturer: n.r.

• Adjustments:
  1. Increments: The dose of active medication will be increased when the PT time is below 1.2 times the control value according to the following restrictions: All increases in dose will be at 1 mg (1/2 tablet) intervals (or less (see for decrements, below)), and will be committeed no more often than every two weeks, although prothrombin time will be determined one week following increment, as well as at two weeks, to determine whether or not the target range has been exceeded.
  2. Decrements: If the PT time exceeds 1.5 times the control value, but is less than 2.0 times control, the daily dose will be reduced by 1/2 tablet (1 mg), with prothrombin time determination at 1 week and 2 weeks following decrement. If the PT time exceeds 2.0 times control value, the taking of the medication will be suspended for three days and then the daily dose will be reduced by 1/2 tablet (1 mg), with PT determinations at 1 week, 2 weeks, and 3 weeks following alteration.
  3. Sequential doses outside opposite boundaries of target range: It may be that an individual's PT, following a 1 mg dose alteration, will go from above the upper limit to below the lower limit or vice-versa within a two week period. If this occurs, an intermediate alternate-day dose adjustment will be instituted, with 1/2 tablets on Monday, Wednesday and Friday.
  4. Noncompliance and dose adjustment: Any patient qualifying as a noncomplier at the time of PT adjustment by having a tablet count discrepancy of more than 10% below predicted count, will not undergo dose adjustment unless the prothrombin time is above the target range, in which case the standard protocol will be used. Any patient with a tablet count discrepancy of more than 10% above target will not undergo dose adjustment unless the prothrombin time is below the target range, in which case the standard protocol will be used.
  5. Interactive medication and dose adjustment: Following initiation, alteration, or termination of any medication known to influence significantly the metabolism or binding of warfarin, PT determinations at one and two weeks will be obtained, with dose adjustment according to protocol.
• Termination criteria: A variety of situations where blinded warfarin/placebo treatment will be either temporarily or permanently unacceptable can be anticipated. In accord with "intention to treat" analysis, all patients so withdrawn from therapy will continue under observation for endpoints until completion of three years. The reason for withdrawal will be recorded in all instances, as will subsequent anticoagulant or antiplatelet therapy.
• Delay between randomization and start of treatment: n.r.

Treatment Blinding

Method of blinding to Warfarin

• Investigator(s)
• Each study center had two study teams: a blinded team consisting of a cardiologist and a neurologist, and a study assistant, and an unblinded team whose members require no constant professional or personal interaction with any of the members of the blinded team.
• Care Provider
• As in blinding of investigators. The person responsible for adjusting doses is unblinded and is not identified to the patients, and is not involved in the regular care of the patient.
• Patient
• All patients told to assume they are anticoagulated.
• Study Nurse
• Yes, as for investigators and provider.

Cointerventions

• Allowed co-interventions: None specified.
• Actual co-interventions administered: None specified.

Outcomes

• Primary Outcome(s): Cerebral Infarction
• Secondary Outcome(s): Cerebral Hemorrhage, Death
• Ancillary Outcome(s): Non-cerebral hemorrhage

Cerebral Infarction (Primary Outcome)

Death (Secondary Outcome)

Side Effects

Major Hemorrhage

Minor Hemorrhage

Outcomes Assessment

Cerebral Infarction (Primary Outcome)

Death (Secondary Outcome)

Schedule of Assessment Activities

Flowchart of Participant Follow-up

Treatment Completion

Compliance

Placebo

• Compliance encouragement method: n.r.
• Compliance checking method: Patient compliance with the assigned dose regimen will be monitored by tablet count, performed by the blinded study assistant at each visit. For this purpose, patients will be required to bring their existing supplies of medication at each visit. These will be turned in at the time of blood sampling and returned at the end of the visit. In the meantime, the tablet count will be performed without the patient's knowledge. A patient taking at least 90% and no more than 110% of his medication will be considered compliant for the purposes of the study, but all patients will be continually encouraged to improve compliance. If the patient fails to bring the study drug bottle to the clinic, a request to do so at the subsequent visit will be made, and a reminder will be mailed to the patient one week before the next clinic visit; dosage adjustment will be made according to prothrombin time results. Patients with persistent poor compliance will not be dropped from the study.
• Actual compliance: 98.08
• Mean Therapeutic Ratio (TR) was 0.994 (sd 0.0442). 53.73% had an average TR < 1.0, and 46.27% had an average TR > 1.0.

Warfarin

• Compliance encouragement method: n.r.
• Compliance checking method: Patient compliance with the assigned dose regimen will be monitored by tablet count, performed by the blinded study assistant at each visit. For this purpose, patients will be required to bring their existing supplies of medication at each visit. These will be turned in at the time of blood sampling and returned at the end of the visit. In the meantime, the tablet count will be performed without the patient's knowledge. A patient taking at least 90% and no more than 110% of his medication will be considered compliant for the purposes of the study, but all patients will be continually encouraged to improve compliance. If the patient fails to bring the study drug bottle to the clinic, a request to do so at the subsequent visit will be made, and a reminder will be mailed to the patient one week before the next clinic visit; dosage adjustment will be made according to prothrombin time results. Patients with persistent poor compliance will not be dropped from the study.
• Actual compliance: 98.16
• Mean Therapeutic Ratio was 1.039 (s.d. 0.0988). 29.41% had average TR <1.2, 55.20% had an average 1.2 <= TR<=1.5, and 15.39% had an average TR > 1.5

Crossovers and Dropouts

Subjects who did not complete their assigned intervention may or may not have been followed for endpoint events.

Comment on intervention completion: Patients who had temporary withdrawal of the assigned intervention are shown here as having completed their assigned intervention. Temporary withdrawals occurred in 91/265 placebo patients and in 98/260 warfarin patients.

Characteristics of Subjects

Results of Primary and Secondary Outcomes

Cerebral Infarction (Primary Outcome)

Cerebral Hemorrhage (Secondary Outcome)

Death (Secondary Outcome)

Kaplan-Meier Model for the Warfarin Group

Comment: Fictitious data, for illustrative purposes only

Cox Proportional Hazards Model

Comment: Fictitious data, for illustrative purposes only

Side Effects

Conclusions

Publications

Total number of publications: 5

Commentary

This trial was cited in these publications:

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